Farkaš Barbara, Minneci Marco, Misevicius Matas, Rozas Isabel
School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse Street, D02 R590 Dublin, Ireland.
Pharmaceuticals (Basel). 2023 Jun 2;16(6):834. doi: 10.3390/ph16060834.
Considering the importance of the 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in the coronavirus disease 2019 (COVID-19) pandemic, an overview of two proteases that play an important role in the infection by SARS-CoV-2, the main protease of SARS-CoV-2 (M) and the host transmembrane protease serine 2 (TMPRSS2), is presented in this review. After summarising the viral replication cycle to identify the relevance of these proteases, the therapeutic agents already approved are presented. Then, this review discusses some of the most recently reported inhibitors first for the viral M and next for the host TMPRSS2 explaining the mechanism of action of each protease. Afterward, some computational approaches to design novel M and TMPRSS2 inhibitors are presented, also describing the corresponding crystallographic structures reported so far. Finally, a brief discussion on a few reports found some dual-action inhibitors for both proteases is given. This review provides an overview of two proteases of different origins (viral and human host) that have become important targets for the development of antiviral agents to treat COVID-19.
鉴于2019年严重急性呼吸综合征冠状病毒2（SARS-CoV-2）爆发导致2019冠状病毒病（COVID-19）大流行的重要性，本综述概述了在SARS-CoV-2感染中起重要作用的两种蛋白酶，即SARS-CoV-2主要蛋白酶（M）和宿主跨膜蛋白酶丝氨酸2（TMPRSS2）。在总结病毒复制周期以确定这些蛋白酶的相关性之后，介绍了已获批的治疗药物。然后，本综述首先讨论了一些最近报道的针对病毒M的抑制剂，接着讨论了针对宿主TMPRSS2的抑制剂，并解释了每种蛋白酶的作用机制。之后，介绍了一些设计新型M和TMPRSS2抑制剂的计算方法，还描述了迄今为止报道的相应晶体结构。最后，简要讨论了一些发现的针对这两种蛋白酶的双效抑制剂的报道。本综述概述了两种不同来源（病毒和人类宿主）的蛋白酶，它们已成为开发治疗COVID-19抗病毒药物的重要靶点。
