A novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), or 2019 novel coronavirus] has been identified as the pathogen of coronavirus disease 2019. The main protease (M^pro, also called 3‐chymotrypsin‐like protease) of SARS‐CoV‐2 is a potential target for treatment of COVID‐19. A M^pro homodimer structure suitable for docking simulations was prepared using a crystal structure (PDB ID: 6Y2G; resolution 2.20 Å). Structural refinement was performed in the presence of peptidomimetic α‐ketoamide inhibitors, which were previously disconnected from each Cys145 of the M^pro homodimer, and energy calculations were performed. Structure‐based virtual screenings were performed using the ChEMBL database. Through a total of 1 485 144 screenings, 64 potential drugs (11 approved, 14 clinical, and 39 preclinical drugs) were predicted to show high binding affinity with M^pro. Additional docking simulations for predicted compounds with high binding affinity with M^pro suggested that 28 bioactive compounds may have potential as effective anti‐SARS‐CoV‐2 drug candidates. The procedure used in this study is a possible strategy for discovering anti‐SARS‐CoV‐2 drugs from drug libraries that may significantly shorten the clinical development period with regard to drug repositioning.

中文翻译：

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通过对ChEMBL数据库进行虚拟筛选，筛选出针对主要冠状病毒蛋白酶的化合物，从而确定了潜在的抗SARS-CoV-2候选药物。

一种新型冠状病毒[严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）或2019年新型冠状病毒]被鉴定为2019年冠状病毒病的病原体。主要蛋白酶（M ^pro，也称为3-胰凝乳蛋白酶样蛋白酶）。 SARS‐CoV‐2的治疗是治疗COVID‐19的潜在目标。AM^亲同二聚体结构使用晶体结构，制备适合于对接模拟（PDB ID：6Y2G;分辨率2.20埃）。在存在拟肽α-酮酰胺抑制剂的情况下进行了结构改进，这些抑制剂先前已与M ^pro的每个Cys145断开连接均二聚体，并进行能量计算。使用ChEMBL数据库进行了基于结构的虚拟筛选。通过总共1 485 144次筛选，预测64种潜在药物（已批准11种，14种临床药物和39种临床前药物）显示出与M ^pro的高结合亲和力。对与M ^pro具有高结合亲和力的预测化合物的其他对接模拟表明，28种生物活性化合物可能具有作为抗SARS-CoV-2有效药物的潜力。本研究中使用的程序是从药物库中发现抗SARS-CoV-2药物的可能策略，这可能会大大缩短药物重新定位的临床开发时间。