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2019冠状病毒病药物再利用计划的综合共识分析

Comprehensive Consensus Analysis of SARS-CoV-2 Drug Repurposing Campaigns.

作者信息

Mslati Hazem, Gentile Francesco, Perez Carl, Cherkasov Artem

机构信息

Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.

出版信息

J Chem Inf Model. 2021 Aug 23;61(8):3771-3788. doi: 10.1021/acs.jcim.1c00384. Epub 2021 Jul 27.

Abstract

The current COVID-19 pandemic has elicited extensive repurposing efforts (both small and large scale) to rapidly identify COVID-19 treatments among approved drugs. Herein, we provide a literature review of large-scale SARS-CoV-2 antiviral drug repurposing efforts and highlight a marked lack of consistent potency reporting. This variability indicates the importance of standardizing best practices-including the use of relevant cell lines, viral isolates, and validated screening protocols. We further surveyed available biochemical and virtual screening studies against SARS-CoV-2 targets (Spike, ACE2, RdRp, PL, and M) and discuss repurposing candidates exhibiting consistent activity across diverse, triaging assays and predictive models. Moreover, we examine repurposed drugs and their efficacy against COVID-19 and the outcomes of representative repurposed drugs in clinical trials. Finally, we propose a drug repurposing pipeline to encourage the implementation of standard methods to fast-track the discovery of candidates and to ensure reproducible results.

摘要

当前的新冠疫情引发了广泛的(无论规模大小)药物重新利用努力,以在已批准的药物中快速识别出针对新冠病毒的治疗方法。在此,我们对大规模的抗SARS-CoV-2病毒药物重新利用努力进行了文献综述,并强调了在效力报告方面明显缺乏一致性。这种变异性表明了规范最佳实践的重要性,包括使用相关细胞系、病毒分离株以及经过验证的筛选方案。我们还调查了针对SARS-CoV-2靶点(刺突蛋白、血管紧张素转换酶2、RNA依赖的RNA聚合酶、木瓜蛋白酶样蛋白酶和膜蛋白)的现有生化和虚拟筛选研究,并讨论了在各种分类分析和预测模型中表现出一致活性的重新利用候选药物。此外,我们研究了重新利用的药物及其对新冠病毒的疗效以及代表性重新利用药物在临床试验中的结果。最后,我们提出了一个药物重新利用流程,以鼓励实施标准方法,快速追踪候选药物的发现并确保结果的可重复性。

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