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

Anoop Narayanan; Shay A Toner; Joyce Jose

doi:10.1042/BST20211180

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

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

Authors

Anoop Narayanan¹, Shay A Toner¹, Joyce Jose^{1

2}

Affiliations

¹ Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, U.S.A.
² Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, U.S.A.

PMID: 35015073
DOI: 10.1042/BST20211180

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.

Keywords: 3CLpro; COVID-19; PLpro; SARS-CoV-2; antiviral; proteases.

Publication types

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

MeSH terms

Antiviral Agents / pharmacology
Drug Design
Drug Repositioning*
Humans
Peptide Hydrolases
Protease Inhibitors / pharmacology*
SARS-CoV-2 / enzymology*
Viral Proteins / antagonists & inhibitors*

Substances

Antiviral Agents
Protease Inhibitors
Viral Proteins
Peptide Hydrolases