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신약개발 데이터셋

신약개발 데이터셋

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● 데이터 상품명 신약개발 데이터셋 ● 데이터 상품 부제 COVID-19의 임상 관련 신약개발 데이터셋 ● 데이터 상품 요약 인용지수 상위 의학저널에 게재된 COVID-19의 신약개발에 관련된 의학 학술논문 데이터 ● 키워드 데이터셋 상품 정보 ■ 상품 설명 및 특징 - 의학논문의 저자 키워드 및 제목과 키워드에서 추출한 키워드에 대하여 키워드 속성, 대역어, 키워드 출처, 논문 DOI, 저자, 발행연월, 논문URL, 저널명, 저널 ISSN, 발행기관, Impact Factor의 정보를 매핑한 데이터 ■ 컬럼(속성) 정보 - 키워드명 : 키워드 - 키워드속성 : 키워드 성격 - 키워드출처 : 키워드 출현 위치 - 키워드대역어 : 자체 보유 의학사전 및 구글번역기에 의한 대역어 - 논문DOI명 : 키워드 출현 논문의 DOI - 논문제목 : 키워드 출현 논문의 제목 - 논문저자 : 키워드 출현 논문의 저자 - 논문발행연월 : 키워드 출현 논문의 발행연월 - 논문초록 : 키워드 출현 논문의 초록 - 논문URL : 키워드 출현 논문의 URL - 저널ISSN명 : 키워드 출현 논문의 저널 ISSN - 저널제목 : 키워드 출현 논문의 저널명 - 저널발행기관명 : 키워드 출현 논문의 발행기관명 ● 연관 데이터셋 상품 정보 ■ 상품 설명 및 특징 - 특정 키워드의 연관 키워드를 co-occurrence 기법과 Latent Semantic Algorithm에 의해 추출한 데이터셋 ■ 컬럼(속성) 정보 - 키워드명 : 키워드 - 키워드속성 : 키워드의 성격 - 연관키워드명 : 키워드와 연관된 키워드 - 연관키워드 속성 : 연관키워드의 속성 - 연관중요도 : 동의여 여부와 동시출현수를 지표로 하는 중요도 ● 기간 및 범위 - 2014년 5월 ~ 2022년 12월 ● 활용 예제 - 특정 주제에 해당되는 키워드의 속성별, 저널별, 연도별, 저자별 추이 - 키워드의 연관어를 속성별, 저널별, 연도별, 저자별 분석

샘플정보
ID
카테고리ID
카테고리명
키워드명
키워드속성
대체키워드명
키워드출처
키워드대역어
논문ID
논문DOI명
논문제목
논문저자
논문발행연월
논문유형
논문출처
논문초록
논문URL
저널ID
저널ISSN명
저널제목
저널발행기관명
저널ImpactFactor명
37097 902 신약개발 these compounds Compound these compound abstract None 14398 10.1371/journal.pone.0269563 Identification of repurposing therapeutics toward SARS-CoV-2 main protease by virtual screening Kamonpan Sanachai@@@Tuanjai Somboon@@@Patcharin Wilasluck@@@Peerapon Deetanya@@@Peter Wolschann@@@Thierry Langer@@@Vannajan Sanghiran Lee@@@Kittikhun Wangkanont@@@Thanyada Rungrotmongkol@@@Supot Hannongbua 202206 Article PMC {{{ Abstract }}} !! SARS-CoV-2 causes the current global pandemic coronavirus disease 2019. Widely-available effective drugs could be a critical factor in halting the pandemic. The main protease (3CLpro) plays a vital role in viral replication; therefore, it is of great interest to find inhibitors for this enzyme. We applied the combination of virtual screening based on molecular docking derived from the crystal structure of the peptidomimetic inhibitors (N3, 13b, and 11a), and experimental verification revealed FDA-approved drugs that could inhibit the 3CLpro of SARS-CoV-2. Three drugs were selected using the binding energy criteria and subsequently performed the 3CLpro inhibition by enzyme-based assay. In addition, six common drugs were also chosen to study the 3CLpro inhibition. Among these compounds, lapatinib showed high efficiency of 3CLpro inhibition (IC50 value of 35 ± 1 μM and Ki of 23 ± 1 μM). The binding behavior of lapatinib against 3CLpro was elucidated by molecular dynamics simulations. This drug could well bind with 3CLpro residues in the five subsites S1', S1, S2, S3, and S4. Moreover, lapatinib's key chemical pharmacophore features toward SAR-CoV-2 3CLpro shared important HBD and HBA with potent peptidomimetic inhibitors. The rational design of lapatinib was subsequently carried out using the obtained results. Our discovery provides an effective repurposed drug and its newly designed analogs to inhibit SARS-CoV-2 3CLpro. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246117/ 49 1932-6203 PLoS ONE San Francisco, CA : Public Library of Science.
37098 902 신약개발 viral replication Term viral replication abstract 바이러스 복제 14398 10.1371/journal.pone.0269563 Identification of repurposing therapeutics toward SARS-CoV-2 main protease by virtual screening Kamonpan Sanachai@@@Tuanjai Somboon@@@Patcharin Wilasluck@@@Peerapon Deetanya@@@Peter Wolschann@@@Thierry Langer@@@Vannajan Sanghiran Lee@@@Kittikhun Wangkanont@@@Thanyada Rungrotmongkol@@@Supot Hannongbua 202206 Article PMC {{{ Abstract }}} !! SARS-CoV-2 causes the current global pandemic coronavirus disease 2019. Widely-available effective drugs could be a critical factor in halting the pandemic. The main protease (3CLpro) plays a vital role in viral replication; therefore, it is of great interest to find inhibitors for this enzyme. We applied the combination of virtual screening based on molecular docking derived from the crystal structure of the peptidomimetic inhibitors (N3, 13b, and 11a), and experimental verification revealed FDA-approved drugs that could inhibit the 3CLpro of SARS-CoV-2. Three drugs were selected using the binding energy criteria and subsequently performed the 3CLpro inhibition by enzyme-based assay. In addition, six common drugs were also chosen to study the 3CLpro inhibition. Among these compounds, lapatinib showed high efficiency of 3CLpro inhibition (IC50 value of 35 ± 1 μM and Ki of 23 ± 1 μM). The binding behavior of lapatinib against 3CLpro was elucidated by molecular dynamics simulations. This drug could well bind with 3CLpro residues in the five subsites S1', S1, S2, S3, and S4. Moreover, lapatinib's key chemical pharmacophore features toward SAR-CoV-2 3CLpro shared important HBD and HBA with potent peptidomimetic inhibitors. The rational design of lapatinib was subsequently carried out using the obtained results. Our discovery provides an effective repurposed drug and its newly designed analogs to inhibit SARS-CoV-2 3CLpro. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246117/ 49 1932-6203 PLoS ONE San Francisco, CA : Public Library of Science.
38054 902 신약개발 SARS-CoV-2 Virus sars-cov-2 author 제2형 중증급성호흡기증후군 코로나바이러스 14518 10.1007/s11427-021-2031-7 Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo Haoran Peng@@@Cuiling Ding@@@Liangliang Jiang@@@Wanda Tang@@@Yan Liu@@@Lanjuan Zhao@@@Zhigang Yi@@@Hao Ren@@@Chong Li@@@Yanhua He@@@Xu Zheng@@@Hailin Tang@@@Zhihui Chen@@@Zhongtian Qi@@@Ping Zhao 202206 Article PMC {{{ Abstract }}} !! The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis. Clinical candidates with high efficacy, ready availability, and that do not develop resistance are in urgent need. Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture, there are few confirmed antiviral candidates in vivo. In this study, 94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs. Among them, 24 compounds with low cytotoxicity were selected, and of these, 17 compounds also effectively suppressed SARS-CoV-2 infection in HeLa cells transduced with human ACE2. Six compounds disturb multiple processes of the SARS-CoV-2 life cycle. Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2 infection. Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant. Except for cisatracurium, six compounds reduced hamster pulmonary viral load, and IL-6 and TNF-α mRNA when assayed at 4 d postinfection. In particular, sertraline, salinomycin, and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro, suggesting promising application for COVID-19 treatment. !!{{ Keywords: }} D614G variant; SARS-CoV-2; drug repurposing; drug resistance; drug screening; hamster model. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713546/ 926 1674-7305 Science China. Life sciences Beijing : Science China Press, co-published with Springer.
37429 902 신약개발 United States Term united state abstract 유나이티드_스테이트_오브_아메리카 14441 10.1111/bph.15452 Therapeutic strategies to fight COVID-19: Which is the status artis? Cristina Scavone@@@Annamaria Mascolo@@@Concetta Rafaniello@@@Liberata Sportiello@@@Ugo Trama@@@Alice Zoccoli@@@Francesca Futura Bernardi@@@Giorgio Racagni@@@Liberato Berrino@@@Giuseppe Castaldo@@@Enrico Coscioni@@@Francesco Rossi@@@Annalisa Capuano 202205 Review PMC {{{ Abstract }}} !! COVID-19 is a complex disease, and many difficulties are faced today especially in the proper choice of pharmacological treatments. The role of antiviral agents for COVID-19 is still being investigated and evidence for immunomodulatory and anti-inflammatory drugs is quite conflicting, whereas the use of corticosteroids is supported by robust evidence. The use of heparins in hospitalized critically ill patients is preferred over other anticoagulants. There are conflicting data on the use of convalescent plasma and vitamin D. According to the World Health Organization (WHO), many vaccines are in Phase III clinical trials, and some of them have already received marketing approval in European countries and in the United States. In conclusion, drug repurposing has represented the main approach recently used in the treatment of patients with COVID-19. At this moment, analysis of efficacy and safety data of drugs and vaccines used in real-life context is strongly needed. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc. !!{{ Keywords: }} clinical research; covid-19; repurposing drugs; review; vaccines. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239658/ 561 0007-1188 British Journal of Pharmacology London : Wiley.
38701 902 신약개발 antiviral therapeutics Term antiviral therapeutic abstract 항 바이러스 치료 14579 10.1021/acs.jcim.1c00524 Drug Repurposing to Identify Nilotinib as a Potential SARS-CoV-2 Main Protease Inhibitor: Insights from a Computational and In Vitro Study Souvik Banerjee@@@Shalini Yadav@@@Sourav Banerjee@@@Sayo O Fakayode@@@Jyothi Parvathareddy@@@Walter Reichard@@@Surekha Surendranathan@@@Foyez Mahmud@@@Ryan Whatcott@@@Joshua Thammathong@@@Bernd Meibohm@@@Duane D Miller@@@Colleen B Jonsson@@@Kshatresh Dutta Dubey 202111 Article PMC {{{ Abstract }}} !! COVID-19, an acute viral pneumonia, has emerged as a devastating pandemic. Drug repurposing allows researchers to find different indications of FDA-approved or investigational drugs. In this current study, a sequence of pharmacophore and molecular modeling-based screening against COVID-19 M pro (PDB: 6LU7) suggested a subset of drugs, from the Drug Bank database, which may have antiviral activity. A total of 44 out of 8823 of the most promising virtual hits from the Drug Bank were subjected to molecular dynamics simulation experiments to explore the strength of their interactions with the SARS-CoV-2 M pro active site. MD findings point toward three drugs (DB04020, DB12411, and DB11779) with very low relative free energies for SARS-CoV-2 M pro with interactions at His41 and Met49. MD simulations identified an additional interaction with Glu166, which enhanced the binding affinity significantly. Therefore, Glu166 could be an interesting target for structure-based drug design. Quantitative structural-activity relationship analysis was performed on the 44 most promising hits from molecular docking-based virtual screening. Partial least square regression accurately predicted the values of independent drug candidates' binding energy with impressively high accuracy. Finally, the EC 50 and CC 50 of 10 drug candidates were measured against SARS-CoV-2 in cell culture. Nilotinib and bemcentinib had EC 50 values of 2.6 and 1.1 μM, respectively. In summary, the results of our computer-aided drug design provide a roadmap for rational drug design of M pro inhibitors and the discovery of certified medications as COVID-19 antiviral therapeutics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547516/ 646 1549-9596 Journal of Chemical Information and Modeling Washington, D.C. : American Chemical Society
46113 902 신약개발 glutathione Drug glutathione abstract None 15973 10.1016/j.mehy.2020.110468 The plausible mechanisms of tramadol for treatment of COVID-19 Nahla E El-Ashmawy@@@Abdel-Halim A Lashin@@@Kamal M Okasha@@@Amal M Abo Kamer@@@Tarek M Mostafa@@@Mona El-Aasr@@@Ahmed E Goda@@@Yusuf A Haggag@@@Haytham O Tawfik@@@Mariam A Abo-Saif 202101 Review PMC {{{ Abstract }}} !! Currently, no single medication has been approved for the management of coronavirus disease-2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, drug repositioningby investigating the use of existing drugs for management of COVID-19 patients is considered a desperate need. Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression. Multiple evidence support that tramadol is a promising drug for treatment of COVID-19 patients. Herein, we discuss the possible beneficial effects of using tramadol against SARS-CoV-2 infection and their underlying mechanism of action. The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2. Recent studies confirmed that COVID-19 patients with acute respiratory failure showed increased fibrin formation and polymerization that may lead to thrombosis. Tramadol owing to its hypocoagulable effect may protect against venous thromboembolism in these patients. Moreover, tramadol can exert a cardioprotective effect via decreasing lactate dehydrogenase (LDH) level which is elevated in most of patients with COVID-19. Furthermore, the severity and mortality of COVID-19 have been correlated with old age patients, which may be due to the lack of antioxidant mechanisms and increased oxidative damage. Tramadol could protect COVID-19 patient from disease complications by increases the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished malondialdehyde. More interestingly, tramadol as an effective analgesic and antitussive may have a beneficial effect on COVID-19 patients suffering from cough, headache, ache, and pain. The tramadol anti-psychotic effect may also protect against psychiatric disorders associated with SARS-CoV-2 infection. Moreover, tramadol has bactericidal activity against a wide range of pathogens including Pseudomonas aeruginosa which is common in severe COVID-19 patients leading to pneumonia with worse clinical outcomes. Therefore, we hypothesize that tramadol might be a promising adjuvant therapeutic option against SARS-CoV-2 infection. Based on that, tramadol should be considered as adjuvant therapy for COVID-19 clinical trials. !!{{ Keywords: }} Anti-inflammatory; COVID-19; Hypocoagulable effect; Immune-enhancing; SARS-CoV-2; Tramadol. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831961/ 2493 0306-9877 Medical Hypotheses Penrith, Eng., Eden Press.
38741 902 신약개발 sequence Term sequence abstract None 14579 10.1021/acs.jcim.1c00524 Drug Repurposing to Identify Nilotinib as a Potential SARS-CoV-2 Main Protease Inhibitor: Insights from a Computational and In Vitro Study Souvik Banerjee@@@Shalini Yadav@@@Sourav Banerjee@@@Sayo O Fakayode@@@Jyothi Parvathareddy@@@Walter Reichard@@@Surekha Surendranathan@@@Foyez Mahmud@@@Ryan Whatcott@@@Joshua Thammathong@@@Bernd Meibohm@@@Duane D Miller@@@Colleen B Jonsson@@@Kshatresh Dutta Dubey 202111 Article PMC {{{ Abstract }}} !! COVID-19, an acute viral pneumonia, has emerged as a devastating pandemic. Drug repurposing allows researchers to find different indications of FDA-approved or investigational drugs. In this current study, a sequence of pharmacophore and molecular modeling-based screening against COVID-19 M pro (PDB: 6LU7) suggested a subset of drugs, from the Drug Bank database, which may have antiviral activity. A total of 44 out of 8823 of the most promising virtual hits from the Drug Bank were subjected to molecular dynamics simulation experiments to explore the strength of their interactions with the SARS-CoV-2 M pro active site. MD findings point toward three drugs (DB04020, DB12411, and DB11779) with very low relative free energies for SARS-CoV-2 M pro with interactions at His41 and Met49. MD simulations identified an additional interaction with Glu166, which enhanced the binding affinity significantly. Therefore, Glu166 could be an interesting target for structure-based drug design. Quantitative structural-activity relationship analysis was performed on the 44 most promising hits from molecular docking-based virtual screening. Partial least square regression accurately predicted the values of independent drug candidates' binding energy with impressively high accuracy. Finally, the EC 50 and CC 50 of 10 drug candidates were measured against SARS-CoV-2 in cell culture. Nilotinib and bemcentinib had EC 50 values of 2.6 and 1.1 μM, respectively. In summary, the results of our computer-aided drug design provide a roadmap for rational drug design of M pro inhibitors and the discovery of certified medications as COVID-19 antiviral therapeutics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547516/ 646 1549-9596 Journal of Chemical Information and Modeling Washington, D.C. : American Chemical Society
38860 902 신약개발 severe disease Disease severe disease abstract None 14592 10.1002/cpt.2603 Innovative Randomized Phase I Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir Ravi Shankar P Singh@@@Sima S Toussi@@@Frances Hackman@@@Phylinda L Chan@@@Rohit Rao@@@Richard Allen@@@Lien Van Eyck@@@Sylvester Pawlak@@@Eugene P Kadar@@@Frances Clark@@@Haihong Shi@@@Annaliesa S Anderson@@@Michael Binks@@@Sandeep Menon@@@Gianluca Nucci@@@Arthur Bergman 202207 Clinical Trial PMC {{{ Abstract }}} !! Coronavirus disease 2019 (COVID-19) is a continued leading cause of hospitalization and death. Safe, efficacious COVID-19 antivirals are needed urgently. Nirmatrelvir (PF-07321332), the first orally bioavailable, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) M pro inhibitor against the coronaviridae family, has demonstrated potent preclinical antiviral activity and benign safety profile. We report safety, tolerability, and pharmacokinetic data of nirmatrelvir with and without ritonavir as a pharmacokinetic enhancer, from an accelerated randomized, double-blind, placebo-controlled, phase I study. Two interleaving single-ascending dose (SAD) cohorts were evaluated in a three-period crossover. Multiple-ascending dose (MAD) with nirmatrelvir/ritonavir twice daily (b.i.d.) dosing was evaluated over 10 days in five parallel cohorts. Safety was assessed, including in a supratherapeutic exposure cohort. Dose and dosing regimen for clinical efficacy evaluation in phase II/III clinical trials were supported by integrating modeling and simulations of SAD/MAD data with nonclinical data and a quantitative systems pharmacology model (QSP). In SAD, MAD, and supratherapeutic exposure cohorts, nirmatrelvir/ritonavir was safe and well-tolerated. Nirmatrelvir exposure and half-life were considerably increased by ritonavir, enabling selection of nirmatrelvir/ritonavir dose and regimen for phase II/III trials (300/100 mg b.i.d.), to achieve concentrations continuously above those required for 90% inhibition of viral replication in vitro. The QSP model suggested that a 5-day regimen would significantly decrease viral load in SARS-CoV-2-infected patients which may prevent development of severe disease, hospitalization, and death. In conclusion, an innovative and seamless trial design expedited establishment of phase I safety and pharmacokinetics of nirmatrelvir/ritonavir, enabling high confidence in phase II/III dose selection and accelerated pivotal trials' initiation ( NCT04756531 ). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087011/ 823 0009-9236 Clinical Pharmacology and Therapeutics Hoboken, NJ : Wiley.
48688 902 신약개발 Analysis Term analysis abstract 분석 16638 10.1016/j.micpath.2021.105114 Host metabolic reprogramming in response to SARS-CoV-2 infection: A systems biology approach S T R Moolamalla@@@Rami Balasubramanian@@@Ruchi Chauhan@@@U Deva Priyakumar@@@P K Vinod 202109 Article PMC {{{ Abstract }}} !! Understanding the pathogenesis of SARS-CoV-2 is essential for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. The influence of SARS-CoV-2 on host metabolism is yet to be fully understood. In this study, we analyzed the transcriptomic data obtained from different human respiratory cell lines and patient samples (nasopharyngeal swab, peripheral blood mononuclear cells, lung biopsy, bronchoalveolar lavage fluid) to understand metabolic alterations in response to SARS-CoV-2 infection. We explored the expression pattern of metabolic genes in the comprehensive genome-scale network model of human metabolism, Recon3D, to extract key metabolic genes, pathways, and reporter metabolites under each SARS-CoV-2-infected condition. A SARS-CoV-2 core metabolic interactome was constructed for network-based drug repurposing. Our analysis revealed the host-dependent dysregulation of glycolysis, mitochondrial metabolism, amino acid metabolism, nucleotide metabolism, glutathione metabolism, polyamine synthesis, and lipid metabolism. We observed different pro- and antiviral metabolic changes and generated hypotheses on how the host metabolism can be targeted for reducing viral titers and immunomodulation. These findings warrant further exploration with more samples and in vitro studies to test predictions. !!{{ Keywords: }} COVID-19; Host-pathogen interaction; Polyamine metabolism; Redox homeostasis; Transcriptomics; Warburg effect. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321700/ 348 0882-4010 Microbial pathogenesis London ; Orlando : Academic Press
52869 902 신약개발 COVID-19 infected patient Term COVID-19 infected patient abstract None 27348 10.1016/j.amsu.2021.102560 Clinical efficacy of Nafamostat Mesylate in combination with Favipiravir for COVID-19 pneumonia treatment review article Maram H. Abduljabbar 202107 Review PMC Alleviation and treatment of the extensive detrimental implications of COVID-19 have materialised into the primary objectives of scientists and virologists along with pathologists assigned with the responsibility of provisioning of care for infected patients. Development and introduction of vaccines have been, till to date, primarily at the prototypical phase. The significance of utilisation of combined drug therapies has been considered to be paramount from the perspective of application of clinical information collected from previous viral epidemics. One prospective treatment application has involved the Multi Drug Therapy (MDT) based approach with utilisation of the combination of drugs Nafamostat Mesylate and Favipiravir with the purpose of reduction of the infectious intensity of COVID-19 viral strain. On account of the extensive prevalence of patients becoming infected with the Novel Coronavirus strain, MDT procedures have been mostly favoured by scientists and clinical virologists with the explicit objective of determination of the probability of such combined drug therapies in terms of assisting the recovery of COVID-19 infected patients. The previous researches conducted on the procedural particulars of treatments regarding effective antidote development for COVID-19 infected patients had brought forth various clinical outcomes on such innovative treatment initiatives concerning the observed effects of MDTs on such patients. The corresponding research literature review endeavour has been oriented towards collecting information regarding 2 specifically utilised medicinal substances (the previously mentioned Nafamostat Mesylate and Favipiravir drugs) for treatment purposes of COVID-19 infected individuals. Such drugs generally are associated with pharmaceutical categories such as antivirals, immune modulators, antibiotics and anticoagulants. These compounds have been utilised in a direct manner by hospital inpatients and such occurrences have permitted the researchers to examine the implications of such drugs on health conditions of COVID-19 patients in laboratory conditions as well. The corresponding study has been responsible for considering the clinical research findings of the combination of such drugs through comparison of observed outcomes. Highlights ? Novel type strain of coronavirus named SARS-CoV-2 is the causative agent of severe respiratory distress named COVID. ? Nafamostat Mesylate and Favipiravir reduce the infectious intensity of SARS-CoV-2 viral strain. ? Favipiravir strongly inhibits the enzyme RNA polymerase. ? Favipiravir was strongly considered to be as the choice for the inhibition of the SARS CoV-2 virus strain. ? Nafamostat Mesylate had anti-inflammatory and anti-coagulation effect in the severe conditions. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277971/ 566 2049-0801 Annals of Medicine and Surgery [Oxford]: Elsevier
65938 902 신약개발 virus Term virus abstract 바이러스 34126 10.1016/j.bcp.2022.115162 JAK inhibition as a new treatment strategy for patients with COVID-19 Jin Huang@@@Chi Zhou@@@Jinniu Deng@@@Jianfeng Zhou 202208 Review article Sciencedirect Abstract!!The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic continues to spread globally. The rapid dispersion of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 drives an urgent need for effective treatments, especially for patients who develop severe pneumonia. The excessive and uncontrolled release of pro-inflammatory cytokines has proved to be an essential factor in the rapidity of disease progression, and some cytokines are significantly associated with adverse outcomes. Most of the upregulated cytokines signal through the Janus kinase?signal transducer and activator of transcription (JAK/STAT) pathway. Therefore, blocking the exaggerated release of cytokines, including IL-2, IL-6, TNF-α, and IFNα/β/γ, by inhibiting JAK/STAT signaling will, presumably, offer favorable pharmacodynamics and present an attractive prospect. JAK inhibitors (JAKi) can also inhibit members of the numb-associated kinase (NAK) family, including AP2-associated kinase 1 (AAK1) and cyclin G-associated kinase (GAK), which regulate the angiotensin-converting enzyme 2 (ACE-2) transmembrane protein and are involved in host viral endocytosis. According to the data released from current clinical trials, JAKi treatment can effectively control the dysregulated cytokine storm and improve clinical outcomes regarding mortality, ICU admission, and discharge. There are still some concerns surrounding thromboembolic events, opportunistic infection such as herpes zoster virus reactivation, and repression of the host’s type-I IFN-dependent immune repair for both viral and bacterial infection. However, the current JAKi clinical trials of COVID-19 raised no new safety concerns except a slightly increased risk of herpes virus infection. In the updated WHO guideline, Baricitinb is strongly recommended as an alternative to IL-6 receptor blockers, particularly in combination with corticosteroids, in patients with severe or critical COVID-19. Future studies will explore the application of JAKi to COVID-19 treatment in greater detail, such as the optimal timing and course of JAKi treatment, individualized medication strategies based on pharmacogenomics, and the effect of combined medications. https://doi.org/10.1016/j.bcp.2022.115162 1433 0006-2952 Biochemical pharmacology Oxford : Elsevier Science.
61253 902 신약개발 was performed Action was performed abstract None 29573 10.1016/j.sxmr.2020.08.006 Could Oral Phosphodiesterase 5 Inhibitors Have a Potential Adjuvant Role in Combating COVID-19 Infection? Taymour Mostafa 202101 Review PMC {{{ Abstract }}} !!{{ Introduction: }} The recent global outbreak of coronavirus disease 2019 (COVID-19) has become a pandemic with a lot of sufferers. Excessive inflammation, exaggerated immune response, with ultimate apoptosis contribute to COVID-19 pathology that progress to acute lung acute respiratory distress. !!{{ Objective: }} To shed a light on the likely bene?ts of the oral phosphodiesterase 5 (PDE5) inhibitor adjuvant role in combating COVID-19 infection. !!{{ Methods: }} A literature review was performed in the PubMed/Medline database, Scopus, Cochrane Library, EMBASE, Academic Search Complete, Google Scholar, and CINAHL databases using the keywords COVID-19; phosphodiesterase-5 inhibitors; cytokine storm; respiratory distress. !!{{ Results: }} Despite the worsening trends of COVID-19, still no drugs are validated to have significant clinical efficacy in the treatment of patients with COVID-19 in large-scale studies. While the progress toward a curative agent and/or vaccine is certainly hopeful, the principal limiting factor in such public health emergencies is always the time. Therefore, a preexisting licensed therapeutic(s) might offer a reprieve to the healthcare systems operating at the edge of capacity. In this context, the innovation of oral PDE5 inhibitors with their valuable effects on erection have provided a breakthrough in the treatment of erectile dysfunction and opened new fields of clinical application for this class of drugs. Oral PDE5 inhibitors have been demonstrated to possess many beneficial useful additional implications with acknowledged anti-inflammatory, antioxidant, immune response regulation, and antiapoptotic properties. These properties have been elucidated through the nitric oxide/soluble guanylyl cyclase/cyclic guanylate monophosphate pathway in addition to the emerged hemeoxygenase-1 enzyme as well as hydrogen sulfide pathways. These properties could support repurposing oral PDE5 inhibitors' potential adjuvant use in targeting different aspects of COVID-19 infection. !!{{ Conclusion: }} Oral PDE5 inhibitors retain several acknowledged off-labeled useful implications with anti-inflammatory, antioxidant, immune response regulation, and antiapoptotic properties. These properties may support repurposing oral PDE5 inhibitors' potential adjuvant use in the protocols combating COVID-19 manifestations. Mostafa T. Could Oral Phosphodiesterase 5 Inhibitors Have a Potential Adjuvant Role in Combating Coronavirus Disease 2019 Infection? Sex Med Rev 2021;9:15-22. !!{{ Keywords: }} COVID-19; PDE5 Inhibitors; SARS-CoV-2; Sildenafil; Tadalafil; Vardenafil. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833179/ 1298 2050-0513 Sexual medicine reviews Amsterdam : Elsevier.
51308 902 신약개발 appear Action appear abstract None 23917 10.1016/j.cmi.2021.10.018 Signals were broadly positive for months, but never definitive: the tocilizumab story Alessandro Cozzi-Lepri@@@Colette Smith@@@Cristina Mussini 202203 Review PMC {{{ Abstract }}} !!{{ Background: }} Most treatment guidelines for coronavirus disease 2019 (COVID-19) currently recommend tocilizumab in combination with dexamethasone in critically ill patients who are exhibiting rapid respiratory decompensation. !!{{ Aims: }} To produce a critical review and summary of the pathway which led to the repurposing of tocilizumab for COVID-19 treatment, from in vitro observations to guidelines recommendations. !!{{ Sources: }} All studies evaluating the effectiveness of tocilizumab to treat COVID-19 disease published between July 2020 and July 2021. !!{{ Content: }} Two large and methodologically well conducted observational studies, the TESEO and the STOP COVID cohorts, showed a reduction in the risk of invasive mechanical ventilation or death in patients treated with tocilizumab as compared to standard of care in 2020. Concomitantly, and up to February 2021, a number of randomized trials (RCTs) with small sample sizes were showing discrepant results. These RCTs had a number of issues: small sample size, various designs and inclusion criteria, and different dosages of tocilizumab used. The confidence interval of the meta-analytic estimate for the RCT results was consistent with the hypothesis of no efficacy of tocilizumab. In our opinion, this was mainly because the meta-analysis included small and heterogeneous studies. These results led to a delay in the inclusion of tocilizumab in guidelines which occurred only in the summer of 2021. !!{{ Implications: }} Although observational studies are unable to control for unmeasured confounding, they can be put together quickly during a pandemic and promptly provide important information. The large sample size allows us to investigate effect measure modifiers and to better target interventions. It is key that the effect size is somewhat large (RR > 2), all sources of bias are properly accounted for, and the direct evidence is weighted against these factors. It appears to us that for tocilizumab, not having dismissed the results of carefully designed and analysed observational studies in 2020 could have prevented many deaths over those months. !!{{ Keywords: }} Covid-19; Evidence-based medicine; Meta-analysis; Propensity score methods; Tocilizumab. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576060/ 884 1198-743X Clinical microbiology and infection : the official London : Elsevier. 3.111
51306 902 신약개발 accounted Action accounted abstract None 23917 10.1016/j.cmi.2021.10.018 Signals were broadly positive for months, but never definitive: the tocilizumab story Alessandro Cozzi-Lepri@@@Colette Smith@@@Cristina Mussini 202203 Review PMC {{{ Abstract }}} !!{{ Background: }} Most treatment guidelines for coronavirus disease 2019 (COVID-19) currently recommend tocilizumab in combination with dexamethasone in critically ill patients who are exhibiting rapid respiratory decompensation. !!{{ Aims: }} To produce a critical review and summary of the pathway which led to the repurposing of tocilizumab for COVID-19 treatment, from in vitro observations to guidelines recommendations. !!{{ Sources: }} All studies evaluating the effectiveness of tocilizumab to treat COVID-19 disease published between July 2020 and July 2021. !!{{ Content: }} Two large and methodologically well conducted observational studies, the TESEO and the STOP COVID cohorts, showed a reduction in the risk of invasive mechanical ventilation or death in patients treated with tocilizumab as compared to standard of care in 2020. Concomitantly, and up to February 2021, a number of randomized trials (RCTs) with small sample sizes were showing discrepant results. These RCTs had a number of issues: small sample size, various designs and inclusion criteria, and different dosages of tocilizumab used. The confidence interval of the meta-analytic estimate for the RCT results was consistent with the hypothesis of no efficacy of tocilizumab. In our opinion, this was mainly because the meta-analysis included small and heterogeneous studies. These results led to a delay in the inclusion of tocilizumab in guidelines which occurred only in the summer of 2021. !!{{ Implications: }} Although observational studies are unable to control for unmeasured confounding, they can be put together quickly during a pandemic and promptly provide important information. The large sample size allows us to investigate effect measure modifiers and to better target interventions. It is key that the effect size is somewhat large (RR > 2), all sources of bias are properly accounted for, and the direct evidence is weighted against these factors. It appears to us that for tocilizumab, not having dismissed the results of carefully designed and analysed observational studies in 2020 could have prevented many deaths over those months. !!{{ Keywords: }} Covid-19; Evidence-based medicine; Meta-analysis; Propensity score methods; Tocilizumab. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576060/ 884 1198-743X Clinical microbiology and infection : the official London : Elsevier. 3.111
56572 902 신약개발 pandemic Term pandemic abstract 범유행_전염병 28918 10.1016/j.metop.2021.100103 Roles of existing drug and drug targets for COVID-19 management Akeberegn Gorems Ayele@@@Engidaw Fentahun Enyew@@@Zemene Demelash Kifle 202106 Article PMC In December 2019, a highly transmissible, pneumonia epidemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), erupted in China and other countries, resulting in devastation and health crisis worldwide currently. The search and using existing drugs support to curb the current highly contagious viral infection is spirally increasing since the pandemic began. This is based on these drugs had against other related RNA-viruses such as MERS?Cov, and SARS-Cov. Moreover, researchers are scrambling to identify novel drug targets and discover novel therapeutic options to vanquish the current pandemic. Since there is no definitive treatment to control Covid-19 vaccines are remain to be a lifeline. Currently, many vaccine candidates are being developed with most of them are reported to have positive results. Therapeutic targets such as helicases, transmembrane serine protease 2, cathepsin L, cyclin G-associated kinase, adaptor-associated kinase 1, two-pore channel, viral virulence factors, 3-chymotrypsin-like protease, suppression of excessive inflammatory response, inhibition of viral membrane, nucleocapsid, envelope, and accessory proteins, and inhibition of endocytosis were identified as a potential target against COVID-19 infection. This review also summarizes plant-based medicines for the treatment of COVID-19 such as saposhnikoviae divaricata, lonicerae japonicae flos, scutellaria baicalensis, lonicera japonicae, and some others. Thus, this review aimed to focus on the most promising therapeutic targets being repurposed against COVID-19 and viral elements that are used in COVID-19 vaccine candidates. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239316/ 763 2589-9368 Metabolism Open [Oxford]: Elsevier Ltd.
52918 902 신약개발 SARS-CoV-2 viral Virus sars-cov-2 viral abstract None 27348 10.1016/j.amsu.2021.102560 Clinical efficacy of Nafamostat Mesylate in combination with Favipiravir for COVID-19 pneumonia treatment review article Maram H. Abduljabbar 202107 Review PMC Alleviation and treatment of the extensive detrimental implications of COVID-19 have materialised into the primary objectives of scientists and virologists along with pathologists assigned with the responsibility of provisioning of care for infected patients. Development and introduction of vaccines have been, till to date, primarily at the prototypical phase. The significance of utilisation of combined drug therapies has been considered to be paramount from the perspective of application of clinical information collected from previous viral epidemics. One prospective treatment application has involved the Multi Drug Therapy (MDT) based approach with utilisation of the combination of drugs Nafamostat Mesylate and Favipiravir with the purpose of reduction of the infectious intensity of COVID-19 viral strain. On account of the extensive prevalence of patients becoming infected with the Novel Coronavirus strain, MDT procedures have been mostly favoured by scientists and clinical virologists with the explicit objective of determination of the probability of such combined drug therapies in terms of assisting the recovery of COVID-19 infected patients. The previous researches conducted on the procedural particulars of treatments regarding effective antidote development for COVID-19 infected patients had brought forth various clinical outcomes on such innovative treatment initiatives concerning the observed effects of MDTs on such patients. The corresponding research literature review endeavour has been oriented towards collecting information regarding 2 specifically utilised medicinal substances (the previously mentioned Nafamostat Mesylate and Favipiravir drugs) for treatment purposes of COVID-19 infected individuals. Such drugs generally are associated with pharmaceutical categories such as antivirals, immune modulators, antibiotics and anticoagulants. These compounds have been utilised in a direct manner by hospital inpatients and such occurrences have permitted the researchers to examine the implications of such drugs on health conditions of COVID-19 patients in laboratory conditions as well. The corresponding study has been responsible for considering the clinical research findings of the combination of such drugs through comparison of observed outcomes. Highlights ? Novel type strain of coronavirus named SARS-CoV-2 is the causative agent of severe respiratory distress named COVID. ? Nafamostat Mesylate and Favipiravir reduce the infectious intensity of SARS-CoV-2 viral strain. ? Favipiravir strongly inhibits the enzyme RNA polymerase. ? Favipiravir was strongly considered to be as the choice for the inhibition of the SARS CoV-2 virus strain. ? Nafamostat Mesylate had anti-inflammatory and anti-coagulation effect in the severe conditions. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277971/ 566 2049-0801 Annals of Medicine and Surgery [Oxford]: Elsevier
56574 902 신약개발 Pneumonia Disease pneumonia abstract 폐렴 28918 10.1016/j.metop.2021.100103 Roles of existing drug and drug targets for COVID-19 management Akeberegn Gorems Ayele@@@Engidaw Fentahun Enyew@@@Zemene Demelash Kifle 202106 Article PMC In December 2019, a highly transmissible, pneumonia epidemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), erupted in China and other countries, resulting in devastation and health crisis worldwide currently. The search and using existing drugs support to curb the current highly contagious viral infection is spirally increasing since the pandemic began. This is based on these drugs had against other related RNA-viruses such as MERS?Cov, and SARS-Cov. Moreover, researchers are scrambling to identify novel drug targets and discover novel therapeutic options to vanquish the current pandemic. Since there is no definitive treatment to control Covid-19 vaccines are remain to be a lifeline. Currently, many vaccine candidates are being developed with most of them are reported to have positive results. Therapeutic targets such as helicases, transmembrane serine protease 2, cathepsin L, cyclin G-associated kinase, adaptor-associated kinase 1, two-pore channel, viral virulence factors, 3-chymotrypsin-like protease, suppression of excessive inflammatory response, inhibition of viral membrane, nucleocapsid, envelope, and accessory proteins, and inhibition of endocytosis were identified as a potential target against COVID-19 infection. This review also summarizes plant-based medicines for the treatment of COVID-19 such as saposhnikoviae divaricata, lonicerae japonicae flos, scutellaria baicalensis, lonicera japonicae, and some others. Thus, this review aimed to focus on the most promising therapeutic targets being repurposed against COVID-19 and viral elements that are used in COVID-19 vaccine candidates. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239316/ 763 2589-9368 Metabolism Open [Oxford]: Elsevier Ltd.
52805 902 신약개발 two groups Patient two group abstract None 27333 10.1016/j.amsu.2021.102867 The utilization of hydroxychloroquine to reduce the main signs and symptoms of COVID-19 patients, a cross-sectional study Salem Alsuwaidan@@@Ziad A. Memish@@@Faisal Alaklobi@@@Kholood Khan@@@Hamdan N. Alajami 202109 Article PMC Hydroxychloroquine (HCQ) and chloroquine were found to have positive results in some non-randomized clinical trials with more benefit in decreasing the viral load of COVID-19. HCQ is a lysosomotropic and lipophilic drug that can penetrate cell membranes, and accumulates in the acidic lysosomes. The high concentration of alkaline HCQ increases the pH in lysosomes from the normal levels of 4.7?4.8 to 6 which leads to inhibition of lysosomes functions and thus, prevents the entry of coronavirus into cells. Objectives The main aim of this study is to find out the appropriateness of using HCQ in asymptomatic/mildly symptomatic COVID-19 positive patients in an attempt to reduce the development of signs and symptoms of COVID-19 and severe disease. Methodology Randomized selection, open-label trial to evaluate the efficacy of HCQ for patients presenting with asymptomatic COVID-19 upon diagnosis. Cases that met the inclusion criteria were divided into two arms [102 subjects to take HCQ (a loading dose of 400?mg twice daily given orally, followed by a maintenance dose of 200?mg twice daily for 4 days), and 100 subjects were used as a control group]. A follow-up for all the participants on daily basis for 14 days for any signs and symptoms (fever, cough, and shortness of breath). The main variables are action profile (represented by Area under the curve (AUC) for fever, cough, and shortness of breath statistically analyzed to differentiate between the two groups. Results Data in this study showed that HCQ was effective in reducing body temperature from the first day to the fifth day; this positive effect was significant with (p?<?0.001) compared with subjects who didn't receive HCQ. While there was no significant effect on cough or Shortness of breath. Conclusion The recommendation of this study is to utilize HCQ to all subjects with asymptomatic COVID-19 infection providing that these subjects are within the inclusion criteria of this study. There was no adverse drug reaction observed for HCQ on daily follow-up. Highlights ? The debate for the use or not to use hydroxychloroquine for COVID-19 patients is still valid. ? A recommendation to utilize HCQ to all subjects with asymptomatic COVID-19 with fever. ? Utilization of HCQ should be within the inclusion criteria of this study. ? It had been noticed that there was no adverse drug reaction observed for HCQ on daily follow-up. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444382/ 566 2049-0801 Annals of Medicine and Surgery [Oxford]: Elsevier
52851 902 신약개발 antivirals Drug antiviral abstract 항바이러스 27348 10.1016/j.amsu.2021.102560 Clinical efficacy of Nafamostat Mesylate in combination with Favipiravir for COVID-19 pneumonia treatment review article Maram H. Abduljabbar 202107 Review PMC Alleviation and treatment of the extensive detrimental implications of COVID-19 have materialised into the primary objectives of scientists and virologists along with pathologists assigned with the responsibility of provisioning of care for infected patients. Development and introduction of vaccines have been, till to date, primarily at the prototypical phase. The significance of utilisation of combined drug therapies has been considered to be paramount from the perspective of application of clinical information collected from previous viral epidemics. One prospective treatment application has involved the Multi Drug Therapy (MDT) based approach with utilisation of the combination of drugs Nafamostat Mesylate and Favipiravir with the purpose of reduction of the infectious intensity of COVID-19 viral strain. On account of the extensive prevalence of patients becoming infected with the Novel Coronavirus strain, MDT procedures have been mostly favoured by scientists and clinical virologists with the explicit objective of determination of the probability of such combined drug therapies in terms of assisting the recovery of COVID-19 infected patients. The previous researches conducted on the procedural particulars of treatments regarding effective antidote development for COVID-19 infected patients had brought forth various clinical outcomes on such innovative treatment initiatives concerning the observed effects of MDTs on such patients. The corresponding research literature review endeavour has been oriented towards collecting information regarding 2 specifically utilised medicinal substances (the previously mentioned Nafamostat Mesylate and Favipiravir drugs) for treatment purposes of COVID-19 infected individuals. Such drugs generally are associated with pharmaceutical categories such as antivirals, immune modulators, antibiotics and anticoagulants. These compounds have been utilised in a direct manner by hospital inpatients and such occurrences have permitted the researchers to examine the implications of such drugs on health conditions of COVID-19 patients in laboratory conditions as well. The corresponding study has been responsible for considering the clinical research findings of the combination of such drugs through comparison of observed outcomes. Highlights ? Novel type strain of coronavirus named SARS-CoV-2 is the causative agent of severe respiratory distress named COVID. ? Nafamostat Mesylate and Favipiravir reduce the infectious intensity of SARS-CoV-2 viral strain. ? Favipiravir strongly inhibits the enzyme RNA polymerase. ? Favipiravir was strongly considered to be as the choice for the inhibition of the SARS CoV-2 virus strain. ? Nafamostat Mesylate had anti-inflammatory and anti-coagulation effect in the severe conditions. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277971/ 566 2049-0801 Annals of Medicine and Surgery [Oxford]: Elsevier
56585 902 신약개발 target Term target abstract 표적 28918 10.1016/j.metop.2021.100103 Roles of existing drug and drug targets for COVID-19 management Akeberegn Gorems Ayele@@@Engidaw Fentahun Enyew@@@Zemene Demelash Kifle 202106 Article PMC In December 2019, a highly transmissible, pneumonia epidemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), erupted in China and other countries, resulting in devastation and health crisis worldwide currently. The search and using existing drugs support to curb the current highly contagious viral infection is spirally increasing since the pandemic began. This is based on these drugs had against other related RNA-viruses such as MERS?Cov, and SARS-Cov. Moreover, researchers are scrambling to identify novel drug targets and discover novel therapeutic options to vanquish the current pandemic. Since there is no definitive treatment to control Covid-19 vaccines are remain to be a lifeline. Currently, many vaccine candidates are being developed with most of them are reported to have positive results. Therapeutic targets such as helicases, transmembrane serine protease 2, cathepsin L, cyclin G-associated kinase, adaptor-associated kinase 1, two-pore channel, viral virulence factors, 3-chymotrypsin-like protease, suppression of excessive inflammatory response, inhibition of viral membrane, nucleocapsid, envelope, and accessory proteins, and inhibition of endocytosis were identified as a potential target against COVID-19 infection. This review also summarizes plant-based medicines for the treatment of COVID-19 such as saposhnikoviae divaricata, lonicerae japonicae flos, scutellaria baicalensis, lonicera japonicae, and some others. Thus, this review aimed to focus on the most promising therapeutic targets being repurposed against COVID-19 and viral elements that are used in COVID-19 vaccine candidates. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239316/ 763 2589-9368 Metabolism Open [Oxford]: Elsevier Ltd.
53132 902 신약개발 appear Action appear abstract None 27480 10.1371/journal.pone.0247109 Non-Adherence Tree Analysis (NATA)?An adherence improvement framework: A COVID-19 case study Ernest Edem Edifor@@@Regina Brown@@@Paul Smith@@@Rick Kossik 202102 Research Article PMC Poor medication adherence is a global phenomenon that has received a significant amount of research attention yet remains largely unsolved. Medication non-adherence can blur drug efficacy results in clinical trials, lead to substantial financial losses, increase the risk of relapse and hospitalisation, or lead to death. The most common methods of measuring adherence are post-treatment measures; that is, adherence is usually measured after the treatment has begun. What the authors are proposing in this multidisciplinary study is a new technique for predicting the factors that are likely to cause non-adherence before or during medication treatment, illustrated in the context of potential non-adherence to COVID-19 antiviral medication. Fault Tree Analysis (FTA), allows system analysts to determine how combinations of simple faults of a system can propagate to cause a total system failure. Monte Carlo simulation is a mathematical algorithm that depends heavily on repeated random sampling to predict the behaviour of a system. In this study, the authors propose a new technique called Non-Adherence Tree Analysis (NATA), based on the FTA and Monte Carlo simulation techniques, to improve adherence. Firstly, the non-adherence factors of a medication treatment lifecycle are translated into what is referred to as a Non-Adherence Tree (NAT). Secondly, the NAT is coded into a format that is translated into the GoldSim software for performing dynamic system modelling and analysis using Monte Carlo. Finally, the GoldSim model is simulated and analysed to predict the behaviour of the NAT. NATA is dynamic and able to learn from emerging datasets to improve the accuracy of future predictions. It produces a framework for improving adherence by analysing social and non-social adherence barriers. Novel terminologies and mathematical expressions have been developed and applied to real-world scenarios. The results of the application of NATA using data from six previous studies in relation to antiviral medication demonstrate a predictive model which suggests that the biggest factor that could contribute to non-adherence to a COVID-19 antiviral treatment is a therapy-related factor (the side effects of the medication). This is closely followed by a condition-related factor (asymptomatic nature of the disease) then patient-related factors (forgetfulness and other causes). From the results, it appears that side effects, asymptomatic factors and forgetfulness contribute 32.44%, 22.67% and 18.22% respectively to discontinuation of medication treatment of COVID-19 antiviral medication treatment. With this information, clinicians can implement relevant interventions and measures and allocate resources appropriately to minimise non-adherence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895356/ 49 1932-6203 PLoS ONE San Francisco, CA : Public Library of Science.
56589 902 신약개발 TPC2, two-pore channel 2 Term TPC2, two-pore channel 2 author None 28918 10.1016/j.metop.2021.100103 Roles of existing drug and drug targets for COVID-19 management Akeberegn Gorems Ayele@@@Engidaw Fentahun Enyew@@@Zemene Demelash Kifle 202106 Article PMC In December 2019, a highly transmissible, pneumonia epidemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), erupted in China and other countries, resulting in devastation and health crisis worldwide currently. The search and using existing drugs support to curb the current highly contagious viral infection is spirally increasing since the pandemic began. This is based on these drugs had against other related RNA-viruses such as MERS?Cov, and SARS-Cov. Moreover, researchers are scrambling to identify novel drug targets and discover novel therapeutic options to vanquish the current pandemic. Since there is no definitive treatment to control Covid-19 vaccines are remain to be a lifeline. Currently, many vaccine candidates are being developed with most of them are reported to have positive results. Therapeutic targets such as helicases, transmembrane serine protease 2, cathepsin L, cyclin G-associated kinase, adaptor-associated kinase 1, two-pore channel, viral virulence factors, 3-chymotrypsin-like protease, suppression of excessive inflammatory response, inhibition of viral membrane, nucleocapsid, envelope, and accessory proteins, and inhibition of endocytosis were identified as a potential target against COVID-19 infection. This review also summarizes plant-based medicines for the treatment of COVID-19 such as saposhnikoviae divaricata, lonicerae japonicae flos, scutellaria baicalensis, lonicera japonicae, and some others. Thus, this review aimed to focus on the most promising therapeutic targets being repurposed against COVID-19 and viral elements that are used in COVID-19 vaccine candidates. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239316/ 763 2589-9368 Metabolism Open [Oxford]: Elsevier Ltd.
69760 902 신약개발 Mild Term mild title,abstract 약한 35179 10.1016/j.jaim.2021.06.009 Repurposing Siddha mercurial drug for mild to moderate COVID-19 ? Case series and exploration of its chemical profile Saravana Shiva@@@Shanmugam Mari@@@Arul Amuthan@@@Ramalingam Shanmugam 202204 Case report Sciencedirect Abstract!!Vajra kandi maathirai (VKM) is a mercury-based traditional Siddha drug used to treat various types of fevers and inflammatory diseases. We report our experience of using VKM successfully in the treatment of 5 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients along with its chemical profile. A family comprising of 5 members, with age ranges between 13 and 77, both male and female, one with pre-existing renal impairment, SARS-CoV-2 positive with mild to moderate category were treated with VKM along with the specific dietary practice. The drug was consumed at home quarantine. Real-Time RT-PCR from oropharynx swab, X-ray/CT scan chest, hematology, renal function, liver function, body temperature, and oxygen saturation were assessed. Blood parameters were repeated after completion of therapy to assess the safety aspect of mercury drug. With the first dose, improvement in the oxygen saturation was observed. Within 3 days of therapy, all symptoms (fever, body pain, cough, and loss of taste) were normalized and the Real-Time RT-PCR was negative for COVID-19. There were no observed side-effects and any damage to kidneys and liver were not observed. Chemical profile of the drug was done using gas chromatography-mass spectrometry and inductively coupled plasma mass spectrometry. The drug contains 22% of mercury along with a 9-Octadecenoic acid-(E), 1H-Imidazole, 4,5-dihydro-2-(phenylmethyl), and 9,12-Octadecadienoic acid (Z,Z)- as major organic compounds. VKM might be a safe drug to manage COVID-19 patients. Rigorous research is required in larger population and also for drug discovery. https://doi.org/10.1016/j.jaim.2021.06.009 2489 0975-9476 Journal of Ayurveda and Integrative Medicine
53661 902 신약개발 time-consuming Term time-consuming abstract None 27729 10.1038/s41598-020-70143-6 In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication Franck Touret@@@Magali Gilles@@@Karine Barral@@@Antoine Nougair?de@@@Jacques van Helden@@@Etienne Decroly@@@Xavier de Lamballerie@@@Bruno Coutard 202008 Article PMC A novel coronavirus, named SARS-CoV-2, emerged in 2019 in China and rapidly spread worldwide. As no approved therapeutics exists to treat COVID-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time-consuming stages of drug development. In this study, we screened the PRESTWICK CHEMICAL LIBRARY composed of 1,520 approved drugs in an infected cell-based assay. The robustness of the screen was assessed by the identification of drugs that already demonstrated in vitro antiviral effect against SARS-CoV-2. Thereby, 90 compounds were identified as positive hits from the screen and were grouped according to their chemical composition and their known therapeutic effect. Then EC50 and CC50 were determined for a subset of 15 compounds from a panel of 23 selected drugs covering the different groups. Eleven compounds such as macrolides antibiotics, proton pump inhibitors, antiarrhythmic agents or CNS drugs emerged showing antiviral potency with 2?<?EC50?≤?20??M. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study provides information for the selection of drugs to be further validated in vivo. Disclaimer: This study corresponds to the early stages of antiviral development and the results do not support by themselves the use of the selected drugs to treat SARS-CoV-2 infection. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403393/ 53 2045-2322 Scientific Reports London : Nature Publishing Group
55195 902 신약개발 Prevent Term prevent abstract abnormality 28140 10.1038/s41398-021-01629-8 Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions Ying Han@@@Kai Yuan@@@Zhe Wang@@@Wei-Jian Liu@@@Zheng-An Lu@@@Lin Liu@@@Le Shi@@@Wei Yan@@@Jun-Liang Yuan@@@Jia-Li Li@@@Jie Shi@@@Zhong-Chun Liu@@@Gao-Hua Wang@@@Thomas Kosten@@@Yan-Ping Bao@@@Lin Lu 202109 Review Article PMC The coronavirus disease 2019 (COVID-19) pandemic has caused large-scale economic and social losses and worldwide deaths. Although most COVID-19 patients have initially complained of respiratory insufficiency, the presence of neuropsychiatric manifestations is also reported frequently, ranging from headache, hyposmia/anosmia, and neuromuscular dysfunction to stroke, seizure, encephalopathy, altered mental status, and psychiatric disorders, both in the acute phase and in the long term. These neuropsychiatric complications have emerged as a potential indicator of worsened clinical outcomes and poor prognosis, thus contributing to mortality in COVID-19 patients. Their etiology remains largely unclear and probably involves multiple neuroinvasive pathways. Here, we summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments. We then discuss the potential therapeutic strategy for intervening and preventing neuropsychiatric complications associated with SARS-CoV-2 infection. Time-series monitoring of clinical?neurochemical?radiological progress of neuropsychiatric and neuroimmune complications need implementation in individuals exposed to SARS-CoV-2. The development of a screening, intervention, and therapeutic framework to prevent and reduce neuropsychiatric sequela is urgently needed and crucial for the short- and long-term recovery of COVID-19 patients. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482959/ 157 2158-3188 Translational Psychiatry New York, NY : Nature Pub. Group.
56169 902 신약개발 searched Action searched abstract None 28811 10.2196/20756 Artificial Intelligence in the Fight Against COVID-19: Scoping Review Alaa Abd-Alrazaq@@@Mohannad Alajlani@@@Dari Alhuwail@@@Jens Schneider@@@Saif Al-Kuwari@@@Zubair Shah@@@Mounir Hamdi@@@Mowafa Househ 202012 Review PMC Background In December 2019, COVID-19 broke out in Wuhan, China, leading to national and international disruptions in health care, business, education, transportation, and nearly every aspect of our daily lives. Artificial intelligence (AI) has been leveraged amid the COVID-19 pandemic; however, little is known about its use for supporting public health efforts. Objective This scoping review aims to explore how AI technology is being used during the COVID-19 pandemic, as reported in the literature. Thus, it is the first review that describes and summarizes features of the identified AI techniques and data sets used for their development and validation. Methods A scoping review was conducted following the guidelines of PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews). We searched the most commonly used electronic databases (eg, MEDLINE, EMBASE, and PsycInfo) between April 10 and 12, 2020. These terms were selected based on the target intervention (ie, AI) and the target disease (ie, COVID-19). Two reviewers independently conducted study selection and data extraction. A narrative approach was used to synthesize the extracted data. Results We considered 82 studies out of the 435 retrieved studies. The most common use of AI was diagnosing COVID-19 cases based on various indicators. AI was also employed in drug and vaccine discovery or repurposing and for assessing their safety. Further, the included studies used AI for forecasting the epidemic development of COVID-19 and predicting its potential hosts and reservoirs. Researchers used AI for patient outcome?related tasks such as assessing the severity of COVID-19, predicting mortality risk, its associated factors, and the length of hospital stay. AI was used for infodemiology to raise awareness to use water, sanitation, and hygiene. The most prominent AI technique used was convolutional neural network, followed by support vector machine. Conclusions The included studies showed that AI has the potential to fight against COVID-19. However, many of the proposed methods are not yet clinically accepted. Thus, the most rewarding research will be on methods promising value beyond COVID-19. More efforts are needed for developing standardized reporting protocols or guidelines for studies on AI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744141/ 88 1439-4456 Journal of Medical Internet Research Toronto : JMIR Publications.
56170 902 신약개발 selected Action selected abstract None 28811 10.2196/20756 Artificial Intelligence in the Fight Against COVID-19: Scoping Review Alaa Abd-Alrazaq@@@Mohannad Alajlani@@@Dari Alhuwail@@@Jens Schneider@@@Saif Al-Kuwari@@@Zubair Shah@@@Mounir Hamdi@@@Mowafa Househ 202012 Review PMC Background In December 2019, COVID-19 broke out in Wuhan, China, leading to national and international disruptions in health care, business, education, transportation, and nearly every aspect of our daily lives. Artificial intelligence (AI) has been leveraged amid the COVID-19 pandemic; however, little is known about its use for supporting public health efforts. Objective This scoping review aims to explore how AI technology is being used during the COVID-19 pandemic, as reported in the literature. Thus, it is the first review that describes and summarizes features of the identified AI techniques and data sets used for their development and validation. Methods A scoping review was conducted following the guidelines of PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews). We searched the most commonly used electronic databases (eg, MEDLINE, EMBASE, and PsycInfo) between April 10 and 12, 2020. These terms were selected based on the target intervention (ie, AI) and the target disease (ie, COVID-19). Two reviewers independently conducted study selection and data extraction. A narrative approach was used to synthesize the extracted data. Results We considered 82 studies out of the 435 retrieved studies. The most common use of AI was diagnosing COVID-19 cases based on various indicators. AI was also employed in drug and vaccine discovery or repurposing and for assessing their safety. Further, the included studies used AI for forecasting the epidemic development of COVID-19 and predicting its potential hosts and reservoirs. Researchers used AI for patient outcome?related tasks such as assessing the severity of COVID-19, predicting mortality risk, its associated factors, and the length of hospital stay. AI was used for infodemiology to raise awareness to use water, sanitation, and hygiene. The most prominent AI technique used was convolutional neural network, followed by support vector machine. Conclusions The included studies showed that AI has the potential to fight against COVID-19. However, many of the proposed methods are not yet clinically accepted. Thus, the most rewarding research will be on methods promising value beyond COVID-19. More efforts are needed for developing standardized reporting protocols or guidelines for studies on AI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744141/ 88 1439-4456 Journal of Medical Internet Research Toronto : JMIR Publications.
56176 902 신약개발 Wuhan, China Institution wuhan, china abstract None 28811 10.2196/20756 Artificial Intelligence in the Fight Against COVID-19: Scoping Review Alaa Abd-Alrazaq@@@Mohannad Alajlani@@@Dari Alhuwail@@@Jens Schneider@@@Saif Al-Kuwari@@@Zubair Shah@@@Mounir Hamdi@@@Mowafa Househ 202012 Review PMC Background In December 2019, COVID-19 broke out in Wuhan, China, leading to national and international disruptions in health care, business, education, transportation, and nearly every aspect of our daily lives. Artificial intelligence (AI) has been leveraged amid the COVID-19 pandemic; however, little is known about its use for supporting public health efforts. Objective This scoping review aims to explore how AI technology is being used during the COVID-19 pandemic, as reported in the literature. Thus, it is the first review that describes and summarizes features of the identified AI techniques and data sets used for their development and validation. Methods A scoping review was conducted following the guidelines of PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews). We searched the most commonly used electronic databases (eg, MEDLINE, EMBASE, and PsycInfo) between April 10 and 12, 2020. These terms were selected based on the target intervention (ie, AI) and the target disease (ie, COVID-19). Two reviewers independently conducted study selection and data extraction. A narrative approach was used to synthesize the extracted data. Results We considered 82 studies out of the 435 retrieved studies. The most common use of AI was diagnosing COVID-19 cases based on various indicators. AI was also employed in drug and vaccine discovery or repurposing and for assessing their safety. Further, the included studies used AI for forecasting the epidemic development of COVID-19 and predicting its potential hosts and reservoirs. Researchers used AI for patient outcome?related tasks such as assessing the severity of COVID-19, predicting mortality risk, its associated factors, and the length of hospital stay. AI was used for infodemiology to raise awareness to use water, sanitation, and hygiene. The most prominent AI technique used was convolutional neural network, followed by support vector machine. Conclusions The included studies showed that AI has the potential to fight against COVID-19. However, many of the proposed methods are not yet clinically accepted. Thus, the most rewarding research will be on methods promising value beyond COVID-19. More efforts are needed for developing standardized reporting protocols or guidelines for studies on AI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744141/ 88 1439-4456 Journal of Medical Internet Research Toronto : JMIR Publications.
56852 902 신약개발 Analysis Term analysis abstract 분석 28938 10.1016/j.csbj.2020.12.033 Novel coronavirus disease (COVID-19) pandemic: A recent mini review Muhammad Fayyaz ur Rehman@@@Chaudhary Fariha@@@Aqsa Anwar@@@Naveed Shahzad@@@Munir Ahmad@@@Salma Mukhtar@@@Muhammad Farhan Ul Haque 202012 Review Article PMC The COVID-19, caused by a novel coronavirus, was declared as a global pandemic by WHO more than five months ago, and we are still experiencing a state of global emergency. More than 74.30 million confirmed cases of the COVID-19 have been reported globally so far, with an average fatality rate of almost 3.0%. Seven different types of coronaviruses had been detected from humans; three of them have resulted in severe outbreaks, i.e., MERS-CoV, SARS-CoV, and SARS-CoV-2. Phylogenetic analysis of the genomes suggests that the possible occurrence of recombination between SARS-like-CoVs from pangolin and bat might have led to the origin of SARS-CoV-2 and the COVID-19 outbreak. Coronaviruses are positive-sense, single-stranded RNA viruses and harbour a genome (30?kb) consisting of two terminal untranslated regions and twelve putative functional open reading frames (ORFs), encoding for non-structural and structural proteins. There are sixteen putative non-structural proteins, including proteases, RNA-dependent RNA polymerase, helicase, other proteins involved in the transcription and replication of SARS-CoV-2, and four structural proteins, including spike protein (S), envelope (E), membrane (M), and nucleocapsid (N). SARS-CoV-2 infection, with a heavy viral load in the body, destroys the human lungs through cytokine storm, especially in elderly persons and people with immunosuppressed disorders. A number of drugs have been repurposed and employed, but still, no specific antiviral medicine has been approved by the FDA to treat this disease. This review provides a current status of the COVID-19, epidemiology, an overview of phylogeny, mode of action, diagnosis, and possible treatment methods and vaccines. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773542/ 2289 2001-0370 Computational and Structural Biotechnology Journal
60159 902 신약개발 viral infectivity Term viral infectivity abstract 바이러스 감염성 29547 10.1080/07391102.2020.1820379 Naltrexone a potential therapeutic candidate for COVID-19 Abhinav Choubey@@@Budheswar Dehury@@@Sunil Kumar@@@Bikash Medhi@@@Prosenjit Mondal 202202 Article PMC {{{ Abstract }}} !! Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease (COVID-19) that has resulted in a global pandemic. At the time of writing, approximately 16.06 million cases have been reported worldwide. Like other coronaviruses, SARS-CoV-2 relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the host receptor Angiotensin-Converting Enzyme2 (ACE2). SARS-CoV-2 infection induces a profound downstream pro-inflammatory cytokine storm. This release of the pro-inflammatory cytokines is underpinning lung tissue damage, respiratory failure, and eventually multiple organ failure in COVID-19 patients. The phosphorylation status of ERK1/2 is positively correlated with virus load and ERK1/2 inhibition suppressed viral replication and viral infectivity. Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2, or damping hyperinflammatory cytokines storm, blocking ERK1/2 phosphorylation have a great potential to inhibit viral entry along with viral infectivity. Herein, we report that the FDA-approved non-peptide opioid antagonist drug, naltrexone suppresses high fat/LPS induced pro-inflammatory cytokine release both from macrophage cells and Adipose Tissue Macrophage. Moreover, Low Dose Naltrexone (LDN) also showed its activity as an ERK1/2 inhibitor. Notably, virtual docking and simulation data also suggest LDN may disrupt the interaction of ACE2 with RBD. LDN may be considered as a target as the treatment and (or) adjuvant therapy for coronavirus infection. Clinical toxicity measurements may not be required for LDN since naltrexone was previously tested and is an approved drug by the FDA.Communicated by Ramaswamy H. Sarma. !!{{ Keywords: }} COVID-19; SARS-CoV-2; drug repurposing; molecular docking; naltrexone; structural bioinformatics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544934/ 219 0739-1102 Journal of biomolecular structure & dynamics June 2012- : Oxon, UK : Taylor & Francis.
61558 902 신약개발 compounds Term compound abstract 화합물 29582 10.1177/2515690X211068826 Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions Tomas Koltai@@@Larry Fliegel 202201 Review PMC {{{ Abstract }}} !! The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture of 6 flavolignan isomers. The 3 more important isomers are silybin (or silibinin), silydianin, and silychristin. Silybin is functionally the most active of these compounds. This group of flavonoids has been extensively studied and they have been used as hepato-protective substances for the mushroom Amanita phalloides intoxication and mainly chronic liver diseases such as alcoholic cirrhosis and nonalcoholic fatty liver. Hepatitis C progression is not, or slightly, modified by silymarin. Recently, it has also been proposed for SARS COVID-19 infection therapy. The biochemical and molecular mechanisms of action of these substances in cancer are subjects of ongoing research. Paradoxically, many of its identified actions such as antioxidant, promoter of ribosomal synthesis, and mitochondrial membrane stabilization, may seem protumoral at first sight, however, silymarin compounds have clear anticancer effects. Some of them are: decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, inducing apoptosis in some malignant cells, and inhibiting promitotic signaling among others. Interestingly, the antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected. Furthermore, there is a long history of silymarin use in human diseases without toxicity after prolonged administration. The ample distribution and easy accessibility to milk thistle-the source of silymarin compounds, its over the counter availability, the fact that it is a weed, some controversial issues regarding bioavailability, and being a nutraceutical rather than a drug, has somehow led medical professionals to view its anticancer effects with skepticism. This is a fundamental reason why it never achieved bedside status in cancer treatment. However, in spite of all the antitumoral effects, silymarin actually has dual effects and in some cases such as pancreatic cancer it can promote stemness. This review deals with recent investigations to elucidate the molecular actions of this flavonoid in cancer, and to consider the possibility of repurposing it. Particular attention is dedicated to silymarin's dual role in cancer and to some controversies of its real effectiveness. !!{{ Keywords: }} antioxidant; cancer; invasion; migration; milk thistle; silybin; silymarin. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814827/ 271 2515-690X Journal of evidence-based integrative medicine [Thousand Oaks, CA] : SAGE Publications
59849 902 신약개발 Drug repurposing Term drug repurposing author 약물 용도 29541 10.1080/23744235.2021.1924397 Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments Shin Jie Yong 202110 Review PMC {{{ Abstract }}} !! Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID. !!{{ Keywords: }} Long-haul COVID-19; drug repurposing; long COVID; pathophysiology; post-COVID-19 syndrome; risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146298/ 1028 2374-4235 Infectious diseases (London, England) London, England : Informa Healthcare
59983 902 신약개발 associations Term association abstract None 29544 10.1093/infdis/jiaa660 Associations Between Genetically Predicted Protein Levels and COVID-19 Severity Jingjing Zhu@@@Chong Wu@@@Lang Wu 202101 Article PMC {{{ Abstract }}} !! It is critical to identify potential causal targets for SARS-CoV-2, which may guide drug repurposing options. We assessed the associations between genetically predicted protein levels and COVID-19 severity. Leveraging data from the COVID-19 Host Genetics Initiative comparing 6492 hospitalized COVID-19 patients and 1 012 809 controls, we identified 18 proteins with genetically predicted levels to be associated with COVID-19 severity at a false discovery rate of &lt;0.05, including 12 that showed an association even after Bonferroni correction. Of the 18 proteins, 6 showed positive associations and 12 showed inverse associations. In conclusion, we identified 18 candidate proteins for COVID-19 severity. !!{{ Keywords: }} COVID-19 severity; genetic instruments; proteins. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797748/ 74 0022-1899 The Journal of Infectious Diseases Oxford : Oxford University Press.
6081 902 신약개발 increase Action increase abstract None 477 10.1186/s13063-020-04928-5 COvid-19 and high-dose VITamin D supplementation TRIAL in high-risk older patients (COVIT-TRIAL): study protocol for a randomized controlled trial 202012 Article PMC Background With the lack of effective therapy, chemoprevention, and vaccination against SARS-CoV-2, focusing on the immediate repurposing of existing drugs gives hope of curbing the COVID-19 pandemic. A recent unbiased genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns. Growing pre-clinical and epidemiological observational data support this assumption. We hypothesized that vitamin D supplementation may improve the prognosis of COVID-19. The aim of this trial is to compare the effect of a single oral high dose of cholecalciferol versus a single oral standard dose on all-cause 14-day mortality rate in COVID-19 older adults at higher risk of worsening. Methods The COVIT-TRIAL study is an open-label, multicenter, randomized controlled superiority trial. Patients aged ≥?65?years with COVID-19 (diagnosed within the preceding 3?days with RT-PCR and/or chest CT scan) and at least one worsening risk factor at the time of inclusion (i.e., age?≥?75?years, or SpO2?≤?94% in room air, or PaO2/FiO2?≤?300?mmHg), having no contraindications to vitamin D supplementation, and having received no vitamin D supplementation >?800 IU/day during the preceding month are recruited. Participants are randomized either to high-dose cholecalciferol (two 200,000?IU drinking vials at once on the day of inclusion) or to standard-dose cholecalciferol (one 50,000?IU drinking vial on the day of inclusion). Two hundred sixty participants are recruited and followed up for 28?days. The primary outcome measure is all-cause mortality within 14?days of inclusion. Secondary outcomes are the score changes on the World Health Organization Ordinal Scale for Clinical Improvement (OSCI) scale for COVID-19, and the between-group comparison of safety. These outcomes are assessed at baseline, day 14, and day 28, together with the serum concentrations of 25(OH)D, creatinine, calcium, and albumin at baseline and day 7. Discussion COVIT-TRIAL is to our knowledge the first randomized controlled trial testing the effect of vitamin D supplementation on the prognosis of COVID-19 in high-risk older patients. High-dose vitamin D supplementation may be an effective, well-tolerated, and easily and immediately accessible treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no scientifically validated treatments. Trial registration ClinicalTrials.gov NCT04344041 . Registered on 14 April 2020 Trial status Recruiting. Recruitment is expected to be completed in April 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768266/ 54 1745-6215 Trials [London] : BioMed Central
61544 902 신약개발 affected Action affected abstract None 29582 10.1177/2515690X211068826 Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions Tomas Koltai@@@Larry Fliegel 202201 Review PMC {{{ Abstract }}} !! The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture of 6 flavolignan isomers. The 3 more important isomers are silybin (or silibinin), silydianin, and silychristin. Silybin is functionally the most active of these compounds. This group of flavonoids has been extensively studied and they have been used as hepato-protective substances for the mushroom Amanita phalloides intoxication and mainly chronic liver diseases such as alcoholic cirrhosis and nonalcoholic fatty liver. Hepatitis C progression is not, or slightly, modified by silymarin. Recently, it has also been proposed for SARS COVID-19 infection therapy. The biochemical and molecular mechanisms of action of these substances in cancer are subjects of ongoing research. Paradoxically, many of its identified actions such as antioxidant, promoter of ribosomal synthesis, and mitochondrial membrane stabilization, may seem protumoral at first sight, however, silymarin compounds have clear anticancer effects. Some of them are: decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, inducing apoptosis in some malignant cells, and inhibiting promitotic signaling among others. Interestingly, the antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected. Furthermore, there is a long history of silymarin use in human diseases without toxicity after prolonged administration. The ample distribution and easy accessibility to milk thistle-the source of silymarin compounds, its over the counter availability, the fact that it is a weed, some controversial issues regarding bioavailability, and being a nutraceutical rather than a drug, has somehow led medical professionals to view its anticancer effects with skepticism. This is a fundamental reason why it never achieved bedside status in cancer treatment. However, in spite of all the antitumoral effects, silymarin actually has dual effects and in some cases such as pancreatic cancer it can promote stemness. This review deals with recent investigations to elucidate the molecular actions of this flavonoid in cancer, and to consider the possibility of repurposing it. Particular attention is dedicated to silymarin's dual role in cancer and to some controversies of its real effectiveness. !!{{ Keywords: }} antioxidant; cancer; invasion; migration; milk thistle; silybin; silymarin. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814827/ 271 2515-690X Journal of evidence-based integrative medicine [Thousand Oaks, CA] : SAGE Publications
70102 902 신약개발 Saliva Term saliva abstract 타액 35192 10.1016/j.encep.2020.05.006 Repurposing chlorpromazine to treat COVID-19: The reCoVery study M. Plaze@@@D. Attali@@@A.-C. Petit@@@M. Blatzer@@@E. Simon-Loriere@@@F. Vinckier@@@A. Cachia@@@F. Chr?tien@@@R. Gaillard 202006 Research article Sciencedirect Abstract!!Objectives!!The ongoing COVID-19 pandemic has caused approximately 2,350,000 infections worldwide and killed more than 160,000 individuals. In Sainte-Anne Hospital (GHU PARIS Psychiatrie & Neuroscience, Paris, France) we have observed a lower incidence of symptomatic forms of COVID-19 among patients than among our clinical staff. This observation led us to hypothesize that psychotropic drugs could have a prophylactic action against SARS-CoV-2 and protect patients from the symptomatic and virulent forms of this infection, since several of these psychotropic drugs have documented antiviral properties. Chlorpromazine (CPZ), a phenothiazine derivative, is also known for its antiviral activity via the inhibition of clathrin-mediated endocytosis. Recentin vitro studies have reported that CPZ exhibits anti-MERS-CoV and anti-SARS-CoV-1 activity.!!Methods!!In this context, the ReCoVery study aims to repurpose CPZ, a molecule with an excellent tolerance profile and a very high biodistribution in the saliva, lungs and brain. We hypothesize that CPZ could reduce the unfavorable course of COVID-19 infection among patients requiring respiratory support without the need for ICU care, and that it could also reduce the contagiousness of SARS-CoV-2. For this purpose, we plan a pilot, multicenter, randomized, single blind, controlled, phase III therapeutic trial (standard treatment vs. CPZ + standard treatment).!!Conclusion!!This repurposing of CPZ for its anti-SARS-CoV-2 activity could offer an alternative, rapid strategy to alleviate infection severity. This repurposing strategy also avoids numerous developmental and experimental steps, and could save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easily managed side effects. https://doi.org/10.1016/j.encep.2020.05.006 2449 0013-7006 L'Enc?phale Paris Masson.
69717 902 신약개발 Safe Term safe abstract 금고 35168 10.1016/S2055-6640(20)30016-9 A review of the safety of favipiravir ? a potential treatment in the COVID-19 pandemic? Victoria Pilkington@@@Toby Pepperrell@@@Andrew Hill 202004 Review article Sciencedirect Abstract!!Background!!Repurposing broad-spectrum antivirals is an immediate treatment opportunity for 2019 coronavirus disease (COVID-19). Favipiravir is an antiviral previously indicated for influenza and Ebola, which has shown some promise in early trials for treatment of COVID-19. We aim to review existing favipiravir safety evidence, which is vital to informing the potential future use of favipiravir in COVID-19.!!Methods!!A search was conducted across EMBASE and MEDLINE databases, supplemented by relevant grey-literature and ClinicalTrials.gov. All studies assessing the use of favipiravir in humans by 27 March 2020 were considered for inclusion. Further analysis of available safety data from phase 2 and 3 studies was undertaken. Data extracted were adverse events (AEs) grade 1?4, serious AEs and discontinuation for AEs. Specific AEs of interest highlighted in early-phase studies, including gastrointestinal AEs and hyperuricaemia, were also examined.!!Results!!Twenty-nine studies were identified as potential sources of evidence of the clinical safety of favipiravir. Six were phase 2 and 3 studies reporting relevant safety data for statistical comparison, representing a total of 4299 participants, an estimated 175 person-years-of-follow-up (PYFU). Comparator drugs were oseltamivir, umifenovir, lopinavir/ritonavir or placebo. Study follow-up was between 5 and 21 days. The proportions of grade 1?4 AEs on favipiravir was 28.2% vs 28.4% (P = n.s.) in the comparison arms. The proportion of discontinuations due to AEs on favipiravir was 1.1% vs 1.2% (P = n.s.) in the comparison arms. For serious AEs the proportion was 0.4% in both arms (P = n.s.). There were significantly fewer gastrointestinal AEs occurring on favipiravir vs comparators [8.7% vs 11.5%; P = 0.003]. Favipiravir showed significantly more uric acid elevations than comparators [5.8% vs 1.3%; P<0.0001].!!Conclusions!!Favipiravir demonstrates a favourable safety profile regarding total and serious AEs. However, safety concerns remain: hyperuricaemia, teratogenicity and QTc prolongation have not yet been adequately studied. Favipiravir may be safe and tolerable in short-term use, but more evidence is needed to assess the longer-term effects of treatment. Given the limitations of the evidence and unresolved safety concerns, caution is warranted in the widespread use of favipiravir against pandemic COVID-19. https://doi.org/10.1016/S2055-6640(20)30016-9 2728 2055-6640 Journal of Virus Eradication
74343 902 신약개발 trials Term trial author 시험 35299 10.1016/j.psc.2021.11.011 Mental Health Clinical Research Innovations during the COVID-19 Pandemic: The Future Is Now Kelly B. Ahern BS@@@Eric J. Lenze MD 202203 Review article Sciencedirect https://doi.org/10.1016/j.psc.2021.11.011 2647 0193-953X Psychiatric Clinics of North America Philadelphia Pa : W B Saunders.
73014 902 신약개발 significantly Action significantly abstract None 35266 10.1016/j.exppara.2021.108124 ‘de Novo’ repurposing of Daflon as anti-intestinal parasitic drug in experimental giardiasis Azza Fahmy@@@Gehan Labib Abuelenain@@@Nesma Rasheed@@@Amr Abdou 202107 Research article Sciencedirect Abstract!!Background!!There is a necessity to develop or discover an alternative drug to combat the drug resistance by Giardia duodenalis and minimize the multiple doses and frequency of the conventional drug administration. Progressive repositioning or ‘repurposing’ of drugs has become widespread due to economic circumstances and medical emergency needs. Daflon 500 mg (DFL) is a natural product used safely as a nutrient supplement and an antidiabetic drug in many European countries and the US.!!Objective!!This study aimed at investigating the efficiency of DFL, in vivo, in a murine model as a safe alternative or co-drug for giardiasis.!!Materials and methods!!Swiss Albino mice (n = 32) were inoculated with 1X104 Giardia cysts and assigned to four groups: One group was the infected non-treated control mice and three experimental groups that were treated differently, either with Metronidazole (MTZ), DFL, or combined therapy of DFL/MTZ. Also, eight normal mice served as a control group. All mice were sacrificed 13 days post-infection for the parasitic, histopathological, and oxidative stress analysis.!!Results!!MTZ, DFL, and the combined therapy significantly reduced the number of trophozoites and cysts compared to their counterparts of the infected mice. The histopathological analysis of the small intestines of the mice treated with the combined therapy retained typical intestinal architecture and normal levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione.!!Conclusion!!This study indicated promising actions of Daflon 500 as an anti-giardial drug, and the results demonstrated its potential effect in improving the intestinal epithelial tissue and disturbing the Giardia stages when it was taken collectively with Metronidazole. https://doi.org/10.1016/j.exppara.2021.108124 2737 0014-4894 Experimental Parasitology Orlando, FL : Academic Press.
76830 902 신약개발 drugs Term drug abstract 약물 35376 10.1016/S2055-6640(20)30017-0 Review of safety and minimum pricing of nitazoxanide for potential treatment of COVID-19 Toby Pepperrell@@@Victoria Pilkington@@@Andrew Owen@@@Junzheng Wang@@@Andrew M. Hill 202004 Review article Sciencedirect Abstract!!Background!!Many treatments are being assessed for repurposing to treat coronavirus disease 2019 (COVID-19). One drug that has shown promising results in vitro is nitazoxanide. Unlike other postulated drugs, nitazoxanide shows a high ratio of maximum plasma concentration (Cmax), after 1 day of 500?mg twice daily (BD), to the concentration required to inhibit 50% replication (EC50) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Cmax: EC50roughly equal to 14:1). As such, it is important to investigate the safety of nitazoxanide for further trials. Furthermore, treatments for COVID-19 should be cheap to promote global access, but prices of many drugs are far higher than the costs of production. We aimed to conduct a review of the safety of nitazoxanide for any prior indication and calculate its minimum costs of production.!!Methods!!A review of nitazoxanide clinical research was conducted using EMBASE and MEDLINE databases, supplemented by ClinicalTrials.gov. We searched for phase 2 or 3 randomised controlled trials (RCTs) comparing nitazoxanide with placebo or active control for 5?14 days in participants experiencing acute infections of any kind. Data extracted were grade 1?4 and serious adverse events (AEs). Data were also extracted on gastrointestinal (GI) AEs, as well as hepatorenal and cardiovascular effects.!!Active pharmaceutical ingredient cost data from 2016 to 2019 were extracted from the Panjiva database and adjusted for 5% loss during production, costs of excipients, formulation, a 10% profit margin and tax. Two dosages, at 500?mg BD and a higher dose of 1100?mg three times daily (TDS), were considered. Our estimated costs were compared with publicly available list prices from a selection of countries.!!Results!!Nine RCTs of nitazoxanide were identified for inclusion. These RCTs accounted for 1514 participants and an estimated 95.3 person-years-of-follow-up. No significant differences were found in any of the AE endpoints assessed, across all trials or on subgroup analyses of active- or placebo-controlled trials. Mild GI AEs increased with dose. No hepatorenal or cardiovascular concerns were raised, but few appropriate metrics were reported. There were no teratogenic concerns, but the evidence base was very limited.!!Based on a weighted-mean cost of US $61/kg, a 14-day course of treatment with nitazoxanide 500?mg BD would cost $1.41. The daily cost would therefore be $0.10. The same 14-day course could cost $3944 in US commercial pharmacies, and $3 per course in Pakistan, India and Bangladesh. At a higher dose of 1100?mg TDS, our estimated cost was $4.08 per 14-day course, equivalent to $0.29 per day.!!Conclusion!!Nitazoxanide demonstrates a good safety profile at approved doses. However, further evidence is required regarding hepatorenal and cardiovascular effects, as well as teratogenicity. We estimate that it would be possible to manufacture nitazoxanide as generic for $1.41 for a 14-day treatment course at 500?mg BD, up to $4.08 at 1100?mg TDS. Further trials in COVID-19 patients should be initiated. If efficacy against SARS-CoV-2 is demonstrated in clinical studies, nitazoxanide may represent a safe and affordable treatment in the ongoing pandemic. https://doi.org/10.1016/S2055-6640(20)30017-0 2728 2055-6640 Journal of Virus Eradication
74489 902 신약개발 Multiorgan Term multiorgan abstract None 35302 10.1016/j.mehy.2020.109883 The association between obesity and poor outcome after COVID-19 indicates a potential therapeutic role for montelukast Muhammad Qutayba Almerie@@@David Daniel Kerrigan 202010 Research article Sciencedirect Abstract!!It is widely believed that infection with the SARS-CoV-2 virus triggers a disproportionate immune response which causes a devastating systemic injury, particularly in individuals with obesity, itself a chronic, multi-organ inflammatory disease. Immune cells accumulate in visceral adipose tissue and together with paracrine adipocytes release a wide range of biologically active cytokines (including IL-1β, IL5, IL6 and IL8) that can result in both local, pulmonary and systemic inflammation. A more intense ‘cytokine storm’ is postulated as the mechanism behind the extreme immune response seen in severe COVID-19.!!It is striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality. Furthermore, patients from a BAME background appear to have increased mortality after SARS-CoV-2 infection; they also have a higher prevalence of central obesity and its metabolic complications.!!In the absence of an effective vaccine, the therapeutic potential of immune-modulating drugs is a priority, but the development of new drugs is expensive and time-consuming. A more pragmatic solution would be to seek to repurpose existing drugs, particularly those that might suppress the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19.!!Montelukast is a cysteinyl leukotriene receptor antagonist licensed to treat asthma and allergic rhinitis. It has been shown to diminish pulmonary response to antigen, tissue eosinophilia and IL-5 expression in inflammatory cells. It has also been shown to decrease elevated levels of IL-1β and IL8 in humans with viral upper respiratory tract infections compared with placebo-treated patients. In addition, in silico studies have demonstrated a high binding affinity of the montelukast molecule to the terminal site of the virus’s main protease enzyme which is needed for virus RNA synthesis and replication.!!Montelukast, which is cheap, safe and widely available would appear to have the potential to be an ideal candidate drug for clinical trials, particularly in early stage disease before irreparable tissue damage has already occurred.!!Hypothesis!!Through a direct anti-viral effect, or by suppression of heightened cytokine release in response to SARS-CoV-2, montelukast will reduce the severity of immune-mediated multiorgan damage resulting from COVID-19, particularly in patients with central obesity and metabolic syndrome. https://doi.org/10.1016/j.mehy.2020.109883 2493 0306-9877 Medical Hypotheses Penrith, Eng., Eden Press.
74490 902 신약개발 obesity Disease obesity title,abstract 비만 35302 10.1016/j.mehy.2020.109883 The association between obesity and poor outcome after COVID-19 indicates a potential therapeutic role for montelukast Muhammad Qutayba Almerie@@@David Daniel Kerrigan 202010 Research article Sciencedirect Abstract!!It is widely believed that infection with the SARS-CoV-2 virus triggers a disproportionate immune response which causes a devastating systemic injury, particularly in individuals with obesity, itself a chronic, multi-organ inflammatory disease. Immune cells accumulate in visceral adipose tissue and together with paracrine adipocytes release a wide range of biologically active cytokines (including IL-1β, IL5, IL6 and IL8) that can result in both local, pulmonary and systemic inflammation. A more intense ‘cytokine storm’ is postulated as the mechanism behind the extreme immune response seen in severe COVID-19.!!It is striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality. Furthermore, patients from a BAME background appear to have increased mortality after SARS-CoV-2 infection; they also have a higher prevalence of central obesity and its metabolic complications.!!In the absence of an effective vaccine, the therapeutic potential of immune-modulating drugs is a priority, but the development of new drugs is expensive and time-consuming. A more pragmatic solution would be to seek to repurpose existing drugs, particularly those that might suppress the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19.!!Montelukast is a cysteinyl leukotriene receptor antagonist licensed to treat asthma and allergic rhinitis. It has been shown to diminish pulmonary response to antigen, tissue eosinophilia and IL-5 expression in inflammatory cells. It has also been shown to decrease elevated levels of IL-1β and IL8 in humans with viral upper respiratory tract infections compared with placebo-treated patients. In addition, in silico studies have demonstrated a high binding affinity of the montelukast molecule to the terminal site of the virus’s main protease enzyme which is needed for virus RNA synthesis and replication.!!Montelukast, which is cheap, safe and widely available would appear to have the potential to be an ideal candidate drug for clinical trials, particularly in early stage disease before irreparable tissue damage has already occurred.!!Hypothesis!!Through a direct anti-viral effect, or by suppression of heightened cytokine release in response to SARS-CoV-2, montelukast will reduce the severity of immune-mediated multiorgan damage resulting from COVID-19, particularly in patients with central obesity and metabolic syndrome. https://doi.org/10.1016/j.mehy.2020.109883 2493 0306-9877 Medical Hypotheses Penrith, Eng., Eden Press.
76143 902 신약개발 risk factor Term risk factor title 위험인자 35355 10.1016/S2665-9913(22)00067-4 Sulfasalazine: a risk factor for severe COVID-19? Maximilian F Konig@@@Katarzyna M Grzes@@@Philip C Robinson@@@Edward J Pearce 202206 Discussion Sciencedirect https://doi.org/10.1016/S2665-9913(22)00067-4 2470 2665-9913 The Lancet Rheumatology
76892 902 신약개발 death Term death abstract 사망 35377 10.1016/j.eclinm.2021.101169 Nafamostat in hospitalized patients with moderate to severe COVID-19 pneumonia: a randomised Phase II clinical trial Sergey V Zhuravel@@@Oleg K Khmelnitskiy@@@Oleg O Burlaka@@@Alexey I Gritsan@@@Boris M Goloshchekin@@@Seieun Kim@@@Ka Young Hong 202110 Research article Sciencedirect ABSTRACT!!Background!!Nafamostat, a serine protease inhibitor, has been used for the treatment of disseminated intravascular coagulation and pancreatitis. In vitro studies and clinical reports suggest its beneficial effect in the treatment of COVID-19 pneumonia.!!Methods!!This phase 2 open-label, randomised, multicentre, controlled trial evaluated nafamostat (4.8 mg/kg/day) plus standard-of-care (SOC) in hospitalised patients with COVID-19 pneumonia (i.e., those requiring nasal high-flow oxygen therapy and/or non-invasive mechanical ventilation). The primary outcome was the time to clinical improvement. Key secondary outcomes included the time to recovery, rates of recovery and National Early Warning Score (NEWS). The trial is registered with ClinicalTrials.gov Identifier: NCT04623021.!!Findings!!A total of 104 patients, mean age 58.6 years were enrolled in 13 clinical centres in Russia between 25/9/2020 and 14/11/2020 and randomised to nafamostat plus SOC (n=53) or SOC alone (n=51). There was no significant difference in time to clinical improvement (primary endpoint) between the nafamostat and SOC groups (median 11 [interquartile range (IQR) 9 to 14) vs 11 [IQR 9 to 14] days; Rate Ratio [RR; the ratio for clinical improvement], 1.00; 95% CI, 0.65 to 1.57; p=0.953). In 36 patients with baseline NEWS ≥7, nafamostat was superior to SOC alone in median time to clinical improvement (11 vs 14 days; RR, 2.89; 95% CI, 1.17 to 7.14; p=0.012). Patients receiving nafamostat in this subgroup had a significantly higher recovery rate compared with SOC alone (61.1% (11/18) vs 11.1 % (2/18) by Day 11, p=0.002). The 28-day mortality was 1.9% (1/52) for nafamostat and 8.0% (4/50) for SOC (95% CI, -17.0 to 3.4; p=0.155). No case of COVID-19 related serious adverse events leading to death was recorded in the patients receiving nafamostat.!!Interpretation!!Our study found no significant difference in time to clinical improvement between the nafamostat and SOC groups, but a shorter median time to clinical improvement in a small group of high-risk COVID-19 patients requiring oxygen treatment. To assess the efficacy further, a larger Phase 3 clinical trial is warranted.!!Funding!!Korea Research Institute of Bioscience and Biotechnology [2020M3A9H5108928] and Chong Kun Dang (CKD) Pharm (Seoul, Korea). https://doi.org/10.1016/j.eclinm.2021.101169 2286 2589-5370 EClinicalMedicine Oxford: Elsevier
77843 902 신약개발 clinical Term clinical title 객관적인 35411 10.1016/j.ijrobp.2020.08.001 An Ounce of Prevention and a Pound of Cure: Randomized Clinical Trials of Therapeutics Against COVID-19 and an Assessment of Personal Protective Equipment and Distancing David J. Sher MD@@@ MPH 202010 Review article Sciencedirect https://doi.org/10.1016/j.ijrobp.2020.08.001 1641 0360-3016 International journal of radiation oncology, biolo New York, NY : Elsevier, Inc.
77457 902 신약개발 history Term history title None 35398 10.1016/j.jaci.2021.12.642 Tocilizumab: History and Future Perspectives in the Era of COVID-19 Rina Modha MD@@@Stuart Novack MD 202202 Conference abstract Sciencedirect https://doi.org/10.1016/j.jaci.2021.12.642 680 0091-6749 The Journal of Allergy and Clinical Immunology St Louis, Mosby.
78324 902 신약개발 Annual Term annual title abnormality 36190 10.1038/s41386-021-01238-5 ACNP 60th Annual Meeting: Poster Abstracts P551 ? P830 202112 Article Nature https://doi.org/10.1038/s41386-021-01238-5 2787 0893-133X Neuropsychopharmacology London : Nature Publishing Group.
48243 902 신약개발 drug Term drug abstract 약물 16229 10.1186/s13063-022-06474-8 Drugs and convalescent plasma therapy for COVID-19: a survey of the interventional clinical studies in Italy after 1 year of pandemic Maria Puopolo@@@Cristina Morciano@@@Maria Buoncervello@@@Chiara De Nuccio@@@Rosa Luisa Potenza@@@Elena Toschi@@@Lucia Palmisano 202206 Article PMC {{{ Abstract }}} !!{{ Background: }} The 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease. !!{{ Methods: }} During an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021. !!{{ Results: }} Ninety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach. !!{{ Conclusions: }} Our study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency. High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic. Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas. !!{{ Keywords: }} COVID-19; Clinical trials; Convalescent plasma; Drugs; Study design; Therapeutic class. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214678/ 54 1745-6215 Trials [London] : BioMed Central
48244 902 신약개발 drugs Term drug author 약물 16229 10.1186/s13063-022-06474-8 Drugs and convalescent plasma therapy for COVID-19: a survey of the interventional clinical studies in Italy after 1 year of pandemic Maria Puopolo@@@Cristina Morciano@@@Maria Buoncervello@@@Chiara De Nuccio@@@Rosa Luisa Potenza@@@Elena Toschi@@@Lucia Palmisano 202206 Article PMC {{{ Abstract }}} !!{{ Background: }} The 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease. !!{{ Methods: }} During an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021. !!{{ Results: }} Ninety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach. !!{{ Conclusions: }} Our study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency. High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic. Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas. !!{{ Keywords: }} COVID-19; Clinical trials; Convalescent plasma; Drugs; Study design; Therapeutic class. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214678/ 54 1745-6215 Trials [London] : BioMed Central
48260 902 신약개발 majority Term majority abstract None 16229 10.1186/s13063-022-06474-8 Drugs and convalescent plasma therapy for COVID-19: a survey of the interventional clinical studies in Italy after 1 year of pandemic Maria Puopolo@@@Cristina Morciano@@@Maria Buoncervello@@@Chiara De Nuccio@@@Rosa Luisa Potenza@@@Elena Toschi@@@Lucia Palmisano 202206 Article PMC {{{ Abstract }}} !!{{ Background: }} The 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease. !!{{ Methods: }} During an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021. !!{{ Results: }} Ninety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach. !!{{ Conclusions: }} Our study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency. High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic. Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas. !!{{ Keywords: }} COVID-19; Clinical trials; Convalescent plasma; Drugs; Study design; Therapeutic class. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214678/ 54 1745-6215 Trials [London] : BioMed Central
29555 902 신약개발 SARS-CoV-2 variants Virus sars-cov-2 variant abstract SARS-COV-2 변이체 10375 10.3389/fimmu.2021.752227 Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics Sriram Kumar@@@Duygu Merve ?alı?kan@@@Josua Janowski@@@Aileen Faist@@@Beate Claudine Gisela Conrad@@@Julius Lange@@@Stephan Ludwig@@@Linda Brunotte 202110 Review PMC Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2 nd Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper the availability of vaccines in many countries. In addition, due to the emergency of SARS-CoV-2 variants with immune escape properties towards the vaccines the global numbers of new infections as well as patients developing severe COVID-19, remains high. New studies reported that about 8% of infected individuals develop long term symptoms with strong personal restrictions on private as well as professional level, which contributes to the long socioeconomic problems caused by this pandemic. Until today, emergency use-approved treatment options for COVID-19 are limited to the antiviral Remdesivir, a nucleoside analogue targeting the viral polymerase, the glucocorticosteroide Dexamethasone as well as neutralizing antibodies. The therapeutic benefits of these treatments are under ongoing debate and clinical studies assessing the efficiency of these treatments are still underway. To identify new therapeutic treatments for COVID-19, now and by the post-pandemic era, diverse experimental approaches are under scientific evaluation in companies and scientific research teams all over the world. To accelerate clinical translation of promising candidates, repurposing approaches of known approved drugs are specifically fostered but also novel technologies are being developed and are under investigation. This review summarizes the recent developments from the lab bench as well as the clinical status of emerging therapeutic candidates and discusses possible therapeutic entry points for the treatment strategies with regard to the biology of SARS-CoV-2 and the clinical course of COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519339/ 109 1664-3224 Frontiers in Immunology [Lausanne : Frontiers Research Foundation].
48261 902 신약개발 Medicine Term medicine abstract 의학 16229 10.1186/s13063-022-06474-8 Drugs and convalescent plasma therapy for COVID-19: a survey of the interventional clinical studies in Italy after 1 year of pandemic Maria Puopolo@@@Cristina Morciano@@@Maria Buoncervello@@@Chiara De Nuccio@@@Rosa Luisa Potenza@@@Elena Toschi@@@Lucia Palmisano 202206 Article PMC {{{ Abstract }}} !!{{ Background: }} The 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease. !!{{ Methods: }} During an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021. !!{{ Results: }} Ninety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach. !!{{ Conclusions: }} Our study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency. High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic. Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas. !!{{ Keywords: }} COVID-19; Clinical trials; Convalescent plasma; Drugs; Study design; Therapeutic class. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214678/ 54 1745-6215 Trials [London] : BioMed Central
48276 902 신약개발 Research Term research abstract 연구 16229 10.1186/s13063-022-06474-8 Drugs and convalescent plasma therapy for COVID-19: a survey of the interventional clinical studies in Italy after 1 year of pandemic Maria Puopolo@@@Cristina Morciano@@@Maria Buoncervello@@@Chiara De Nuccio@@@Rosa Luisa Potenza@@@Elena Toschi@@@Lucia Palmisano 202206 Article PMC {{{ Abstract }}} !!{{ Background: }} The 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease. !!{{ Methods: }} During an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021. !!{{ Results: }} Ninety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach. !!{{ Conclusions: }} Our study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency. High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic. Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas. !!{{ Keywords: }} COVID-19; Clinical trials; Convalescent plasma; Drugs; Study design; Therapeutic class. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214678/ 54 1745-6215 Trials [London] : BioMed Central
59839 902 신약개발 cognitive Term cognitive abstract None 29541 10.1080/23744235.2021.1924397 Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments Shin Jie Yong 202110 Review PMC {{{ Abstract }}} !! Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID. !!{{ Keywords: }} Long-haul COVID-19; drug repurposing; long COVID; pathophysiology; post-COVID-19 syndrome; risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146298/ 1028 2374-4235 Infectious diseases (London, England) London, England : Informa Healthcare
59840 902 신약개발 conditions Term condition abstract None 29541 10.1080/23744235.2021.1924397 Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments Shin Jie Yong 202110 Review PMC {{{ Abstract }}} !! Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID. !!{{ Keywords: }} Long-haul COVID-19; drug repurposing; long COVID; pathophysiology; post-COVID-19 syndrome; risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146298/ 1028 2374-4235 Infectious diseases (London, England) London, England : Informa Healthcare
59841 902 신약개발 cough Symptom cough abstract 기침 29541 10.1080/23744235.2021.1924397 Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments Shin Jie Yong 202110 Review PMC {{{ Abstract }}} !! Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID. !!{{ Keywords: }} Long-haul COVID-19; drug repurposing; long COVID; pathophysiology; post-COVID-19 syndrome; risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146298/ 1028 2374-4235 Infectious diseases (London, England) London, England : Informa Healthcare
60105 902 신약개발 bioinformatics Term bioinformatic abstract 생물정보학 29547 10.1080/07391102.2020.1820379 Naltrexone a potential therapeutic candidate for COVID-19 Abhinav Choubey@@@Budheswar Dehury@@@Sunil Kumar@@@Bikash Medhi@@@Prosenjit Mondal 202202 Article PMC {{{ Abstract }}} !! Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease (COVID-19) that has resulted in a global pandemic. At the time of writing, approximately 16.06 million cases have been reported worldwide. Like other coronaviruses, SARS-CoV-2 relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the host receptor Angiotensin-Converting Enzyme2 (ACE2). SARS-CoV-2 infection induces a profound downstream pro-inflammatory cytokine storm. This release of the pro-inflammatory cytokines is underpinning lung tissue damage, respiratory failure, and eventually multiple organ failure in COVID-19 patients. The phosphorylation status of ERK1/2 is positively correlated with virus load and ERK1/2 inhibition suppressed viral replication and viral infectivity. Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2, or damping hyperinflammatory cytokines storm, blocking ERK1/2 phosphorylation have a great potential to inhibit viral entry along with viral infectivity. Herein, we report that the FDA-approved non-peptide opioid antagonist drug, naltrexone suppresses high fat/LPS induced pro-inflammatory cytokine release both from macrophage cells and Adipose Tissue Macrophage. Moreover, Low Dose Naltrexone (LDN) also showed its activity as an ERK1/2 inhibitor. Notably, virtual docking and simulation data also suggest LDN may disrupt the interaction of ACE2 with RBD. LDN may be considered as a target as the treatment and (or) adjuvant therapy for coronavirus infection. Clinical toxicity measurements may not be required for LDN since naltrexone was previously tested and is an approved drug by the FDA.Communicated by Ramaswamy H. Sarma. !!{{ Keywords: }} COVID-19; SARS-CoV-2; drug repurposing; molecular docking; naltrexone; structural bioinformatics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544934/ 219 0739-1102 Journal of biomolecular structure & dynamics June 2012- : Oxon, UK : Taylor & Francis.
81465 902 신약개발 reported Action reported abstract None 78187 10.3390/ijms231911009 Virtual Screening and Quantum Chemistry Analysis for SARS-CoV-2 RNA-Dependent RNA Polymerase Using the ChEMBL Database: Reproduction of the Remdesivir-RTP and Favipiravir-RTP Binding Modes Obtained from Cryo-EM Experiments with High Binding Affinity Motonori Tsuji 202209 Article PMC {{{ Abstract }}} !! The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the pathogenic cause of coronavirus disease 2019 (COVID-19). The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is a potential target for the treatment of COVID-19. An RdRp complex:dsRNA structure suitable for docking simulations was prepared using a cryo-electron microscopy (cryo-EM) structure (PDB ID: 7AAP; resolution, 2.60 ?) that was reported recently. Structural refinement was performed using energy calculations. Structure-based virtual screening was performed using the ChEMBL database. Through 1,838,257 screenings, 249 drugs (37 approved, 93 clinical, and 119 preclinical drugs) were predicted to exhibit a high binding affinity for the RdRp complex:dsRNA. Nine nucleoside triphosphate analogs with anti-viral activity were included among these hit drugs, and among them, remdesivir-ribonucleoside triphosphate and favipiravir-ribonucleoside triphosphate adopted a similar docking mode as that observed in the cryo-EM structure. Additional docking simulations for the predicted compounds with high binding affinity for the RdRp complex:dsRNA suggested that 184 bioactive compounds could be anti-SARS-CoV-2 drug candidates. The hit bioactive compounds mainly consisted of a typical noncovalent major groove binder for dsRNA. Three-layer ONIOM (MP2/6-31G:AM1:AMBER) geometry optimization calculations and frequency analyses (MP2/6-31G:AMBER) were performed to estimate the binding free energy of a representative bioactive compound obtained from the docking simulation, and the fragment molecular orbital calculation at the MP2/6-31G level of theory was subsequently performed for analyzing the detailed interactions. The procedure used in this study represents a possible strategy for discovering anti-SARS-CoV-2 drugs from drug libraries that could significantly shorten the clinical development period for drug repositioning. !!{{ Keywords: }} COVID-19; ONIOM geometry optimization calculation; RNA-dependent RNA polymerase; SARS-CoV-2; drug repositioning; fragment molecular orbital calculation; frequency analysis; quantum chemistry calculation; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570209/ 170 1422-0067 International Journal of Molecular Sciences Basel, Switzerland : MDPI
81487 902 신약개발 candidate Term candidate title None 78200 10.3390/molecules27185988 In Silico Study towards Repositioning of FDA-Approved Drug Candidates for Anticoronaviral Therapy: Molecular Docking, Molecular Dynamics and Binding Free Energy Calculations Wesam S Qayed@@@Rafaela S Ferreira@@@Jos? Rog?rio A Silva 202209 Article PMC {{{ Abstract }}} !! The SARS-CoV-2 targets were evaluated for a set of FDA-approved drugs using a combination of drug repositioning and rigorous computational modeling methodologies such as molecular docking and molecular dynamics (MD) simulations followed by binding free energy calculations. Six FDA-approved drugs including, Ouabain, Digitoxin, Digoxin, Proscillaridin, Salinomycin and Niclosamide with promising anti-SARS-CoV-2 activity were screened in silico against four SARS-CoV-2 proteins-papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), SARS-CoV-2 main protease (Mpro), and adaptor-associated kinase 1 (AAK1)-in an attempt to define their promising targets. The applied computational techniques suggest that all the tested drugs exhibited excellent binding patterns with higher scores and stable complexes compared to the native protein cocrystallized inhibitors. Ouabain was suggested to act as a dual inhibitor for both PLpro and Mpro enzymes, while Digitoxin bonded perfectly to RdRp. In addition, Salinomycin targeted PLpro. Particularly, Niclosamide was found to target AAK1 with greater affinity compared to the reference drug. Our study provides comprehensive molecular-level insights for identifying or designing novel anti-COVID-19 drugs. !!{{ Keywords: }} anti-COVID-19; binding free energy; drug repositioning; molecular docking; molecular dynamic simulations. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505381/ 186 1420-3049 Molecules Basel, Switzerland : MDPI
81645 902 신약개발 computational drug discovery Term computational drug discovery author None 78318 10.1111/cbdd.14136 A review on computer-aided chemogenomics and drug repositioning for rational COVID-19 drug discovery Saeid Maghsoudi@@@Bahareh Taghavi Shahraki@@@Fatemeh Rameh@@@Masoomeh Nazarabi@@@Yousef Fatahi@@@Omid Akhavan@@@Mohammad Rabiee@@@Ebrahim Mostafavi@@@Eder C Lima@@@Mohammad Reza Saeb@@@Navid Rabiee 202211 Article PMC {{{ Abstract }}} !! Application of materials capable of energy harvesting to increase the efficiency and environmental adaptability is sometimes reflected in the ability of discovery of some traces in an environment-either experimentally or computationally-to enlarge practical application window. The emergence of computational methods, particularly computer-aided drug discovery (CADD), provides ample opportunities for the rapid discovery and development of unprecedented drugs. The expensive and time-consuming process of traditional drug discovery is no longer feasible, for nowadays the identification of potential drug candidates is much easier for therapeutic targets through elaborate in silico approaches, allowing the prediction of the toxicity of drugs, such as drug repositioning (DR) and chemical genomics (chemogenomics). Coronaviruses (CoVs) are cross-species viruses that are able to spread expeditiously from the into new host species, which in turn cause epidemic diseases. In this sense, this review furnishes an outline of computational strategies and their applications in drug discovery. A special focus is placed on chemogenomics and DR as unique and emerging system-based disciplines on CoV drug and target discovery to model protein networks against a library of compounds. Furthermore, to demonstrate the special advantages of CADD methods in rapidly finding a drug for this deadly virus, numerous examples of the recent achievements grounded on molecular docking, chemogenomics, and DR are reported, analyzed, and interpreted in detail. It is believed that the outcome of this review assists developers of energy harvesting materials and systems for detection of future unexpected kinds of CoVs or other variants. !!{{ Keywords: }} Covid-19; chemogenomics; computational drug discovery; coronavirus disease; drug repositioning; polypharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539342/ 421 1747-0277 Chemical biology & drug design Oxford : Wiley-Blackwell
81644 902 신약개발 Computational drug Term computational drug abstract None 78318 10.1111/cbdd.14136 A review on computer-aided chemogenomics and drug repositioning for rational COVID-19 drug discovery Saeid Maghsoudi@@@Bahareh Taghavi Shahraki@@@Fatemeh Rameh@@@Masoomeh Nazarabi@@@Yousef Fatahi@@@Omid Akhavan@@@Mohammad Rabiee@@@Ebrahim Mostafavi@@@Eder C Lima@@@Mohammad Reza Saeb@@@Navid Rabiee 202211 Article PMC {{{ Abstract }}} !! Application of materials capable of energy harvesting to increase the efficiency and environmental adaptability is sometimes reflected in the ability of discovery of some traces in an environment-either experimentally or computationally-to enlarge practical application window. The emergence of computational methods, particularly computer-aided drug discovery (CADD), provides ample opportunities for the rapid discovery and development of unprecedented drugs. The expensive and time-consuming process of traditional drug discovery is no longer feasible, for nowadays the identification of potential drug candidates is much easier for therapeutic targets through elaborate in silico approaches, allowing the prediction of the toxicity of drugs, such as drug repositioning (DR) and chemical genomics (chemogenomics). Coronaviruses (CoVs) are cross-species viruses that are able to spread expeditiously from the into new host species, which in turn cause epidemic diseases. In this sense, this review furnishes an outline of computational strategies and their applications in drug discovery. A special focus is placed on chemogenomics and DR as unique and emerging system-based disciplines on CoV drug and target discovery to model protein networks against a library of compounds. Furthermore, to demonstrate the special advantages of CADD methods in rapidly finding a drug for this deadly virus, numerous examples of the recent achievements grounded on molecular docking, chemogenomics, and DR are reported, analyzed, and interpreted in detail. It is believed that the outcome of this review assists developers of energy harvesting materials and systems for detection of future unexpected kinds of CoVs or other variants. !!{{ Keywords: }} Covid-19; chemogenomics; computational drug discovery; coronavirus disease; drug repositioning; polypharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539342/ 421 1747-0277 Chemical biology & drug design Oxford : Wiley-Blackwell
81655 902 신약개발 drugs Term drug abstract 약물 78318 10.1111/cbdd.14136 A review on computer-aided chemogenomics and drug repositioning for rational COVID-19 drug discovery Saeid Maghsoudi@@@Bahareh Taghavi Shahraki@@@Fatemeh Rameh@@@Masoomeh Nazarabi@@@Yousef Fatahi@@@Omid Akhavan@@@Mohammad Rabiee@@@Ebrahim Mostafavi@@@Eder C Lima@@@Mohammad Reza Saeb@@@Navid Rabiee 202211 Article PMC {{{ Abstract }}} !! Application of materials capable of energy harvesting to increase the efficiency and environmental adaptability is sometimes reflected in the ability of discovery of some traces in an environment-either experimentally or computationally-to enlarge practical application window. The emergence of computational methods, particularly computer-aided drug discovery (CADD), provides ample opportunities for the rapid discovery and development of unprecedented drugs. The expensive and time-consuming process of traditional drug discovery is no longer feasible, for nowadays the identification of potential drug candidates is much easier for therapeutic targets through elaborate in silico approaches, allowing the prediction of the toxicity of drugs, such as drug repositioning (DR) and chemical genomics (chemogenomics). Coronaviruses (CoVs) are cross-species viruses that are able to spread expeditiously from the into new host species, which in turn cause epidemic diseases. In this sense, this review furnishes an outline of computational strategies and their applications in drug discovery. A special focus is placed on chemogenomics and DR as unique and emerging system-based disciplines on CoV drug and target discovery to model protein networks against a library of compounds. Furthermore, to demonstrate the special advantages of CADD methods in rapidly finding a drug for this deadly virus, numerous examples of the recent achievements grounded on molecular docking, chemogenomics, and DR are reported, analyzed, and interpreted in detail. It is believed that the outcome of this review assists developers of energy harvesting materials and systems for detection of future unexpected kinds of CoVs or other variants. !!{{ Keywords: }} Covid-19; chemogenomics; computational drug discovery; coronavirus disease; drug repositioning; polypharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539342/ 421 1747-0277 Chemical biology & drug design Oxford : Wiley-Blackwell
81654 902 신약개발 drug repositioning Term drug repositioning author 약물 재배치 78318 10.1111/cbdd.14136 A review on computer-aided chemogenomics and drug repositioning for rational COVID-19 drug discovery Saeid Maghsoudi@@@Bahareh Taghavi Shahraki@@@Fatemeh Rameh@@@Masoomeh Nazarabi@@@Yousef Fatahi@@@Omid Akhavan@@@Mohammad Rabiee@@@Ebrahim Mostafavi@@@Eder C Lima@@@Mohammad Reza Saeb@@@Navid Rabiee 202211 Article PMC {{{ Abstract }}} !! Application of materials capable of energy harvesting to increase the efficiency and environmental adaptability is sometimes reflected in the ability of discovery of some traces in an environment-either experimentally or computationally-to enlarge practical application window. The emergence of computational methods, particularly computer-aided drug discovery (CADD), provides ample opportunities for the rapid discovery and development of unprecedented drugs. The expensive and time-consuming process of traditional drug discovery is no longer feasible, for nowadays the identification of potential drug candidates is much easier for therapeutic targets through elaborate in silico approaches, allowing the prediction of the toxicity of drugs, such as drug repositioning (DR) and chemical genomics (chemogenomics). Coronaviruses (CoVs) are cross-species viruses that are able to spread expeditiously from the into new host species, which in turn cause epidemic diseases. In this sense, this review furnishes an outline of computational strategies and their applications in drug discovery. A special focus is placed on chemogenomics and DR as unique and emerging system-based disciplines on CoV drug and target discovery to model protein networks against a library of compounds. Furthermore, to demonstrate the special advantages of CADD methods in rapidly finding a drug for this deadly virus, numerous examples of the recent achievements grounded on molecular docking, chemogenomics, and DR are reported, analyzed, and interpreted in detail. It is believed that the outcome of this review assists developers of energy harvesting materials and systems for detection of future unexpected kinds of CoVs or other variants. !!{{ Keywords: }} Covid-19; chemogenomics; computational drug discovery; coronavirus disease; drug repositioning; polypharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539342/ 421 1747-0277 Chemical biology & drug design Oxford : Wiley-Blackwell
81837 902 신약개발 disrupt Action disrupt abstract None 78867 10.3390/molecules27207034 Griseofulvin: An Updated Overview of Old and Current Knowledge Parisa Aris@@@Yulong Wei@@@Masoud Mohamadzadeh@@@Xuhua Xia 202210 Article PMC {{{ Abstract }}} !! Griseofulvin is an antifungal polyketide metabolite produced mainly by ascomycetes. Since it was commercially introduced in 1959, griseofulvin has been used in treating dermatophyte infections. This fungistatic has gained increasing interest for multifunctional applications in the last decades due to its potential to disrupt mitosis and cell division in human cancer cells and arrest hepatitis C virus replication. In addition to these inhibitory effects, we and others found griseofulvin may enhance ACE2 function, contribute to vascular vasodilation, and improve capillary blood flow. Furthermore, molecular docking analysis revealed that griseofulvin and its derivatives have good binding potential with SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), and spike protein receptor-binding domain (RBD), suggesting its inhibitory effects on SARS-CoV-2 entry and viral replication. These findings imply the repurposing potentials of the FDA-approved drug griseofulvin in designing and developing novel therapeutic interventions. In this review, we have summarized the available information from its discovery to recent progress in this growing field. Additionally, explored is the possible mechanism leading to rare hepatitis induced by griseofulvin. We found that griseofulvin and its metabolites, including 6-desmethylgriseofulvin (6-DMG) and 4- desmethylgriseofulvin (4-DMG), have favorable interactions with cytokeratin intermediate filament proteins (K8 and K18), ranging from -3.34 to -5.61 kcal mol -1 . Therefore, they could be responsible for liver injury and Mallory body (MB) formation in hepatocytes of human, mouse, and rat treated with griseofulvin. Moreover, the stronger binding of griseofulvin to K18 in rodents than in human may explain the observed difference in the severity of hepatitis between rodents and human. !!{{ Keywords: }} SARS-CoV-2; dermatophytic fungi; drug repurposing; griseofulvin; griseofulvin derivatives; gsf gene cluster; polyketide compound; spindle microtubule. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9610072/ 186 1420-3049 Molecules Basel, Switzerland : MDPI
82397 902 신약개발 Volume Term volume abstract None 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82379 902 신약개발 hERG. Term herg author None 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82377 902 신약개발 Giant Term giant title abnormality 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82378 902 신약개발 global pandemic Term global pandemic abstract 전 세계 감염병 세계적 유행 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82375 902 신약개발 effort Term effort abstract None 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82376 902 신약개발 FDA Institution fda abstract FDA 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82369 902 신약개발 assessments Term assessment abstract None 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82374 902 신약개발 drug Term drug abstract 약물 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82364 902 신약개발 Annual Term annual abstract abnormality 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82368 902 신약개발 article Term article abstract None 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82362 902 신약개발 Abstract Term abstract abstract None 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82363 902 신약개발 Analysis Term analysis abstract 분석 78879 10.1016/j.vascn.2022.107206 Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment Michael K Pugsley@@@Yevgeniya E Koshman@@@Tessa de Korte@@@Simon Authier@@@Brett R Winters@@@Michael J Curtis 202209 Article PMC {{{ Abstract }}} !! The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the comprehensive in vitro proarrhythmia assay (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve? !!{{ Keywords: }} ICHE14/S7B; QT correction; Regulatory; Safety pharmacology; hERG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356617/ 2654 1056-8719 Journal of Pharmacological and Toxicological Methods New York, NY : Elsevier, c1992-.
82361 902 신약개발 Virtual screening Term virtual screening abstract 가상 심사 78878 10.3389/fcimb.2022.929430 In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective Md Mominur Rahman@@@Md Rezaul Islam@@@Shopnil Akash@@@Sadia Afsana Mim@@@Md Saidur Rahaman@@@Talha Bin Emran@@@Esra K?peli Akkol@@@Rohit Sharma@@@Fahad A Alhumaydhi@@@Sherouk Hussein Sweilam@@@Md Emon Hossain@@@Tanmay Kumar Ray@@@Sharifa Sultana@@@Muniruddin Ahmed@@@Eduardo Sobarzo-S?nchez@@@Polrat Wilairatana 202208 Article PMC {{{ Abstract }}} !! The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases. !!{{ Keywords: }} COVID-19; SARS-CoV-2; alkaloids; drug design; natural products; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441699/ 206 2235-2988 Frontiers in Cellular and Infection Microbiology Lausanne : Frontiers Media SA.
82360 902 신약개발 virtual screening. Term virtual screening author 가상 심사 78878 10.3389/fcimb.2022.929430 In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective Md Mominur Rahman@@@Md Rezaul Islam@@@Shopnil Akash@@@Sadia Afsana Mim@@@Md Saidur Rahaman@@@Talha Bin Emran@@@Esra K?peli Akkol@@@Rohit Sharma@@@Fahad A Alhumaydhi@@@Sherouk Hussein Sweilam@@@Md Emon Hossain@@@Tanmay Kumar Ray@@@Sharifa Sultana@@@Muniruddin Ahmed@@@Eduardo Sobarzo-S?nchez@@@Polrat Wilairatana 202208 Article PMC {{{ Abstract }}} !! The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases. !!{{ Keywords: }} COVID-19; SARS-CoV-2; alkaloids; drug design; natural products; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441699/ 206 2235-2988 Frontiers in Cellular and Infection Microbiology Lausanne : Frontiers Media SA.
82359 902 신약개발 viral replication Term viral replication abstract 바이러스 복제 78878 10.3389/fcimb.2022.929430 In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective Md Mominur Rahman@@@Md Rezaul Islam@@@Shopnil Akash@@@Sadia Afsana Mim@@@Md Saidur Rahaman@@@Talha Bin Emran@@@Esra K?peli Akkol@@@Rohit Sharma@@@Fahad A Alhumaydhi@@@Sherouk Hussein Sweilam@@@Md Emon Hossain@@@Tanmay Kumar Ray@@@Sharifa Sultana@@@Muniruddin Ahmed@@@Eduardo Sobarzo-S?nchez@@@Polrat Wilairatana 202208 Article PMC {{{ Abstract }}} !! The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases. !!{{ Keywords: }} COVID-19; SARS-CoV-2; alkaloids; drug design; natural products; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441699/ 206 2235-2988 Frontiers in Cellular and Infection Microbiology Lausanne : Frontiers Media SA.
82358 902 신약개발 vaccination Term vaccination abstract 백신 접종 78878 10.3389/fcimb.2022.929430 In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective Md Mominur Rahman@@@Md Rezaul Islam@@@Shopnil Akash@@@Sadia Afsana Mim@@@Md Saidur Rahaman@@@Talha Bin Emran@@@Esra K?peli Akkol@@@Rohit Sharma@@@Fahad A Alhumaydhi@@@Sherouk Hussein Sweilam@@@Md Emon Hossain@@@Tanmay Kumar Ray@@@Sharifa Sultana@@@Muniruddin Ahmed@@@Eduardo Sobarzo-S?nchez@@@Polrat Wilairatana 202208 Article PMC {{{ Abstract }}} !! The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases. !!{{ Keywords: }} COVID-19; SARS-CoV-2; alkaloids; drug design; natural products; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441699/ 206 2235-2988 Frontiers in Cellular and Infection Microbiology Lausanne : Frontiers Media SA.
82357 902 신약개발 Treatment Treatment treatment abstract 치료 78878 10.3389/fcimb.2022.929430 In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective Md Mominur Rahman@@@Md Rezaul Islam@@@Shopnil Akash@@@Sadia Afsana Mim@@@Md Saidur Rahaman@@@Talha Bin Emran@@@Esra K?peli Akkol@@@Rohit Sharma@@@Fahad A Alhumaydhi@@@Sherouk Hussein Sweilam@@@Md Emon Hossain@@@Tanmay Kumar Ray@@@Sharifa Sultana@@@Muniruddin Ahmed@@@Eduardo Sobarzo-S?nchez@@@Polrat Wilairatana 202208 Article PMC {{{ Abstract }}} !! The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases. !!{{ Keywords: }} COVID-19; SARS-CoV-2; alkaloids; drug design; natural products; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441699/ 206 2235-2988 Frontiers in Cellular and Infection Microbiology Lausanne : Frontiers Media SA.
82356 902 신약개발 Toxicity Term toxicity abstract 독성 78878 10.3389/fcimb.2022.929430 In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective Md Mominur Rahman@@@Md Rezaul Islam@@@Shopnil Akash@@@Sadia Afsana Mim@@@Md Saidur Rahaman@@@Talha Bin Emran@@@Esra K?peli Akkol@@@Rohit Sharma@@@Fahad A Alhumaydhi@@@Sherouk Hussein Sweilam@@@Md Emon Hossain@@@Tanmay Kumar Ray@@@Sharifa Sultana@@@Muniruddin Ahmed@@@Eduardo Sobarzo-S?nchez@@@Polrat Wilairatana 202208 Article PMC {{{ Abstract }}} !! The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases. !!{{ Keywords: }} COVID-19; SARS-CoV-2; alkaloids; drug design; natural products; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441699/ 206 2235-2988 Frontiers in Cellular and Infection Microbiology Lausanne : Frontiers Media SA.
82355 902 신약개발 took place Action took place abstract None 78878 10.3389/fcimb.2022.929430 In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective Md Mominur Rahman@@@Md Rezaul Islam@@@Shopnil Akash@@@Sadia Afsana Mim@@@Md Saidur Rahaman@@@Talha Bin Emran@@@Esra K?peli Akkol@@@Rohit Sharma@@@Fahad A Alhumaydhi@@@Sherouk Hussein Sweilam@@@Md Emon Hossain@@@Tanmay Kumar Ray@@@Sharifa Sultana@@@Muniruddin Ahmed@@@Eduardo Sobarzo-S?nchez@@@Polrat Wilairatana 202208 Article PMC {{{ Abstract }}} !! The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases. !!{{ Keywords: }} COVID-19; SARS-CoV-2; alkaloids; drug design; natural products; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441699/ 206 2235-2988 Frontiers in Cellular and Infection Microbiology Lausanne : Frontiers Media SA.
82354 902 신약개발 therapeutic target Term therapeutic target abstract None 78878 10.3389/fcimb.2022.929430 In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective Md Mominur Rahman@@@Md Rezaul Islam@@@Shopnil Akash@@@Sadia Afsana Mim@@@Md Saidur Rahaman@@@Talha Bin Emran@@@Esra K?peli Akkol@@@Rohit Sharma@@@Fahad A Alhumaydhi@@@Sherouk Hussein Sweilam@@@Md Emon Hossain@@@Tanmay Kumar Ray@@@Sharifa Sultana@@@Muniruddin Ahmed@@@Eduardo Sobarzo-S?nchez@@@Polrat Wilairatana 202208 Article PMC {{{ Abstract }}} !! The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases. !!{{ Keywords: }} COVID-19; SARS-CoV-2; alkaloids; drug design; natural products; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441699/ 206 2235-2988 Frontiers in Cellular and Infection Microbiology Lausanne : Frontiers Media SA.
82353 902 신약개발 therapeutic molecules Term therapeutic molecule abstract None 78878 10.3389/fcimb.2022.929430 In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective Md Mominur Rahman@@@Md Rezaul Islam@@@Shopnil Akash@@@Sadia Afsana Mim@@@Md Saidur Rahaman@@@Talha Bin Emran@@@Esra K?peli Akkol@@@Rohit Sharma@@@Fahad A Alhumaydhi@@@Sherouk Hussein Sweilam@@@Md Emon Hossain@@@Tanmay Kumar Ray@@@Sharifa Sultana@@@Muniruddin Ahmed@@@Eduardo Sobarzo-S?nchez@@@Polrat Wilairatana 202208 Article PMC {{{ Abstract }}} !! The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases. !!{{ Keywords: }} COVID-19; SARS-CoV-2; alkaloids; drug design; natural products; virtual screening. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441699/ 206 2235-2988 Frontiers in Cellular and Infection Microbiology Lausanne : Frontiers Media SA.
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