Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43606, USA.
Laboratory of Genome Integrity and Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
Drug Discov Today. 2021 Mar;26(3):804-816. doi: 10.1016/j.drudis.2020.12.005. Epub 2020 Dec 9.
The coronavirus disease 2019 (COVID-19) pandemic has prompted an urgent need for new treatment strategies. No target-specific drugs are currently available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but new drug candidates targeting the viral replication cycle are being explored. A prime target of drug-discovery efforts is the SARS-CoV-2 main protease (M). The main proteases of different coronaviruses, including SARS-CoV-2, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), share a structurally conserved substrate-binding region that can be exploited to design new protease inhibitors. With the recent reporting of the X-ray crystal structure of the SARS-CoV-2 M, studies to discover M inhibitors using both virtual and in vitro screening are progressing rapidly. This review focusses on the recent developments in the search for small-molecule inhibitors targeting the SARS-CoV-2 M.
2019 年冠状病毒病（COVID-19）大流行促使人们迫切需要新的治疗策略。目前，针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）还没有特效药物，但针对病毒复制周期的新药候选物正在探索中。药物发现的主要目标是 SARS-CoV-2 主蛋白酶（Mpro）。不同冠状病毒（包括 SARS-CoV-2、SARS-CoV 和中东呼吸综合征冠状病毒（MERS-CoV））的主蛋白酶都具有结构保守的底物结合区域，可以利用该区域来设计新型蛋白酶抑制剂。随着 SARS-CoV-2 M 的 X 射线晶体结构的最新报道，使用虚拟和体外筛选发现 M 抑制剂的研究正在迅速推进。本综述重点介绍了针对 SARS-CoV-2 M 的小分子抑制剂的最新研究进展。
