Perspectives On SARS-CoV-2 Main Protease Inhibitors

Authors

Kaifu Gao, Michigan State University
Rui Wang, Michigan State University
Jiahui Chen, Michigan State University
Jetze J. Tepe, Michigan State University
Faqing Huang, University of Southern MississippiFollow
Guo Wei Wei, Michigan State University

Document Type

Article

Publication Date

11-19-2021

Department

Chemistry and Biochemistry

School

Mathematics and Natural Sciences

Abstract

The main protease (M^pro) 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^pro 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^pro 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^pro inhibitors for SARS-CoV-2 and future coronavirus diseases.

Publication Title

Journal of Medicinal Chemistry

Volume

64

Issue

23

First Page

16922

Last Page

16955

Recommended Citation

Gao, K., Wang, R., Chen, J., Tepe, J., Huang, F., Wei, G. (2021). Perspectives On SARS-CoV-2 Main Protease Inhibitors. Journal of Medicinal Chemistry, 64(23), 16922-16955.
Available at: https://aquila.usm.edu/fac_pubs/19490