Kuo Chih-Jung, Chao Tai-Ling, Kao Han-Chieh, Tsai Ya-Min, Liu Yi-Kai, Wang Lily Hui-Ching, Hsieh Ming-Chang, Chang Sui-Yuan, Liang Po-Huang
Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
Antimicrob Agents Chemother. 2021 Mar 18;65(4). doi: 10.1128/AAC.02577-20.
Coronavirus (CoV) disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed many lives worldwide and is still spreading since December 2019. The 3C-like protease (3CL) and papain-like protease (PL) are essential for maturation of viral polyproteins in SARS-CoV-2 life cycle and thus regarded as key drug targets for the disease. In this study, 3CL and PL assay platforms were established, and their substrate specificities were characterized. The assays were used to screen collections of 1,068 and 2,701 FDA-approved drugs. After excluding the externally used drugs which are too toxic, we totally identified 12 drugs as 3CL inhibitors and 36 drugs as PL inhibitors active at 10 μM. Among these inhibitors, six drugs were found to suppress SARS-CoV-2 with the half-maximal effective concentration (EC) below or close to 10 μM. This study enhances our understanding on the proteases and provides FDA-approved drugs for prevention and/or treatment of COVID-19.
2019年冠状病毒病（COVID-19）由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起，自2019年12月以来已在全球夺走许多生命，且仍在传播。3C样蛋白酶（3CL）和木瓜样蛋白酶（PL）在SARS-CoV-2生命周期中对病毒多聚蛋白的成熟至关重要，因此被视为该疾病的关键药物靶点。在本研究中建立了3CL和PL检测平台，并对其底物特异性进行了表征。这些检测用于筛选1068种和2701种美国食品药品监督管理局（FDA）批准的药物。在排除毒性过大的外用药物后，我们共鉴定出12种药物为3CL抑制剂，36种药物为在10μM时具有活性的PL抑制剂。在这些抑制剂中，发现有6种药物能抑制SARS-CoV-2，其半数最大有效浓度（EC）低于或接近10μM。本研究增进了我们对这些蛋白酶的理解，并为预防和/或治疗COVID-19提供了FDA批准的药物。
