Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
Department of Veterinary Medicine, National Chung Hsing University, Taichung 40227, Taiwan.
Bioorg Med Chem Lett. 2021 Jun 15;42:128067. doi: 10.1016/j.bmcl.2021.128067. Epub 2021 May 3.
The outbreak of coronavirus (CoV) disease 2019 (COVID-19) caused by the severe acute respiratory syndrome CoV-2 (SARS-CoV-2) has turned into a pandemic. The enzyme 3C-like protease (3CL) is essential for the maturation of viral polyproteins in SARS-CoV-2 and is therefore regarded as a key drug target for treating the disease. To identify 3CL inhibitors that can suppress SARS-CoV-2 replication, we performed a virtual screening of 500,282 compounds in a Korean compound bank. We then subjected the top computational hits to inhibitory assays against 3CL in vitro, leading to the identification of a class of non-covalent inhibitors. Among these inhibitors, compound 7 showed an EC of 39.89 μM against SARS-CoV-2 and CC of 453.5 μM. This study provides candidates for the optimization of potent 3CL inhibitors showing antiviral effects against SARS-CoV-2.
由严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）爆发已经成为一种大流行。3C 样蛋白酶（3CL）对于 SARS-CoV-2 中病毒多蛋白的成熟至关重要，因此被认为是治疗该疾病的关键药物靶点。为了鉴定能够抑制 SARS-CoV-2 复制的 3CL 抑制剂，我们对韩国化合物库中的 500,282 种化合物进行了虚拟筛选。然后，我们对体外 3CL 的抑制试验进行了计算命中的前处理，从而鉴定出一类非共价抑制剂。在这些抑制剂中，化合物 7 对 SARS-CoV-2 的 EC 为 39.89 μM，CC 为 453.5 μM。本研究为优化具有抗 SARS-CoV-2 抗病毒作用的强效 3CL 抑制剂提供了候选物。
