Structural biology of SARS-CoV-2 Mpro and drug discovery

Yinkai Duan; Haofeng Wang; Zhenghong Yuan; Haitao Yang

doi:10.1016/j.sbi.2023.102667

Structural biology of SARS-CoV-2 M^pro and drug discovery

Curr Opin Struct Biol. 2023 Oct:82:102667. doi: 10.1016/j.sbi.2023.102667. Epub 2023 Aug 4.

Authors

Yinkai Duan¹, Haofeng Wang¹, Zhenghong Yuan², Haitao Yang³

Affiliations

¹ Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Shanghai Clinical Research and Trial Center, Shanghai, China.
² Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Institute of Infectious Disease and Biosecurity, Shanghai Medical College of Fudan University, Shanghai, China. Electronic address: zhyuan@shmu.edu.cn.
³ Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Shanghai Clinical Research and Trial Center, Shanghai, China. Electronic address: yanght@shanghaitech.edu.cn.

PMID: 37544112
DOI: 10.1016/j.sbi.2023.102667

Abstract

Since its outbreak in late 2019, the COVID-19 pandemic has drawn enormous attention worldwide as a consequence of being the most disastrous infectious disease in the past century. As one of the most immediately druggable targets of SARS-CoV-2, the main protease (M^pro) has been studied thoroughly. In this review, we provide a comprehensive summary of recent advances in structural studies of M^pro, which provide new knowledge about M^pro in terms of its biological function, structural characteristics, substrate specificity, and autocleavage process. We examine the remarkable strides made in targeting M^pro for drug discovery during the pandemic. We summarize insights into the current understanding of the structural features of M^pro and the discovery of existing M^pro-targeting drugs, illuminating pathways for the future development of anti-SARS-CoV-2 therapeutics.

Keywords: Autocleavage; Drug discovery; Main protease; SARS-CoV-2; Structural studies.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / chemistry
Antiviral Agents / pharmacology
Biology
COVID-19*
Drug Discovery
Humans
Molecular Docking Simulation
Pandemics
Protease Inhibitors / chemistry
Protease Inhibitors / metabolism
Protease Inhibitors / pharmacology
SARS-CoV-2* / metabolism

Substances

Antiviral Agents
Protease Inhibitors