Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods
Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods
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通过计算方法分析 SARS-CoV-2 的治疗靶点并发现潜在药物
DOI：
10.1016/j.apsb.2020.02.008
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发表时间：
2020-05-01
影响因子：
14.5
通讯作者：
Li, Hua
中科院分区：
文献类型：
--
作者：
Wu, Canrong;Liu, Yang;Li, Hua
SARS-CoV-2已造成数万人感染和1000多人死亡。目前还没有注册的治疗冠状病毒感染的疗法。由于新药研发过程的耗时，药物重新定位可能是解决突发传染病流行的唯一方法。我们对SARS-CoV-2基因编码的所有蛋白质进行了系统分析，将其与其他冠状病毒的蛋白质进行了比较，预测了它们的结构，并建立了19个可通过同源建模完成的结构。通过基于靶点的虚拟配体筛选，从包括锌药物数据库和我们自己的天然产物数据库在内的化合物文库中筛选了21个靶点(包括两个人类靶点)。详细讨论了重要靶标3-糜蛋白酶样酶(3CLpro)、SPEKE、依赖于RNA的RNA聚合酶(RdRp)和木瓜蛋白酶样酶(PLPro)的结构和筛选结果。此外，还建立了78种常用抗病毒药物的数据库，其中包括目前市场上正在进行SARS-CoV-2临床试验的药物。预测了这些化合物的可能靶点和作用于特定靶点的潜在药物。这项研究将为进一步的SARS-CoV-2体外和体内研究提供新的先导化合物和靶点，为目前正在进行的临床研究提供新的见解，并可能为治疗SARS-CoV-2感染的药物重新定位提供新的策略。(C)中国医学科学院中国药学会、药物所2020年。爱思唯尔B.V.制作和主办。
SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used antiviral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.