Perspectives on SARS-CoV-2 Main Protease Inhibitors

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2021 Nov 20

PMID 34798775

Citations 38

Authors

Kaifu Gao

Rui Wang

Jiahui Chen

Jetze J Tepe

Faqing Huang

Guo-Wei Wei

Affiliations

Soon will be listed here.

Abstract

The main protease (M) plays a crucial role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and is highly conserved, rendering it one of the most attractive therapeutic targets for SARS-CoV-2 inhibition. Currently, although two drug candidates targeting SARS-CoV-2 M designed by Pfizer are under clinical trials, no SARS-CoV-2 medication is approved due to the long period of drug development. Here, we collect a comprehensive list of 817 available SARS-CoV-2 and SARS-CoV M inhibitors from the literature or databases and analyze their molecular mechanisms of action. The structure-activity relationships (SARs) among each series of inhibitors are discussed. Additionally, we broadly examine available antiviral activity, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and animal tests of these inhibitors. We comment on their druggability or drawbacks that prevent them from becoming drugs. This Perspective sheds light on the future development of M inhibitors for SARS-CoV-2 and future coronavirus diseases.

Citing Articles

Research Progress on the Structure and Function, Immune Escape Mechanism, Antiviral Drug Development Methods, and Clinical Use of SARS-CoV-2 M.

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Amino acid T25 in the substrate-binding domain of SARS-CoV-2 nsp5 is involved in viral replication in the mouse lung.

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Ma Z, Li W, Shen Y, Xu Y, Liu G, Chang J Nat Methods. 2024; 22(1):102-112.

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