基于结构的抑制剂设计和重新利用临床药物靶向 SARS-CoV-2 蛋白酶。

Structure-based inhibitor design and repurposing clinical drugs to target SARS-CoV-2 proteases.

机构信息

Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, U.S.A.

Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, U.S.A.

出版信息

Biochem Soc Trans. 2022 Feb 28;50(1):151-165. doi: 10.1042/BST20211180.

DOI:10.1042/BST20211180

PMID:35015073

Abstract

SARS-CoV-2, the coronavirus responsible for the current COVID-19 pandemic, encodes two proteases, 3CLpro and PLpro, two of the main antiviral research targets. Here we provide an overview of the structures and functions of 3CLpro and PLpro and examine strategies of structure-based drug designing and drug repurposing against these proteases. Rational structure-based drug design enables the generation of potent and target-specific antivirals. Drug repurposing offers an attractive prospect with an accelerated turnaround. Thus far, several protease inhibitors have been identified, and some candidates are undergoing trials that may well prove to be effective antivirals against SARS-CoV-2.

摘要

SARS-CoV-2，即引发当前 COVID-19 大流行的冠状病毒，编码两种蛋白酶，3CLpro 和 PLpro，这是两个主要的抗病毒研究靶点。本文概述了 3CLpro 和 PLpro 的结构和功能，并探讨了基于结构的药物设计和药物再利用策略。合理的基于结构的药物设计可以产生高效且靶向特定的抗病毒药物。药物再利用提供了一个有吸引力的前景，可以加速开发。迄今为止，已经鉴定出几种蛋白酶抑制剂，一些候选药物正在进行临床试验，这些药物很可能成为针对 SARS-CoV-2 的有效抗病毒药物。