2. Academic Validation
  3. Perspectives on SARS-CoV-2 Main Protease Inhibitors

Perspectives on SARS-CoV-2 Main Protease Inhibitors

  • J Med Chem. 2021 Dec 9;64(23):16922-16955. doi: 10.1021/acs.jmedchem.1c00409.
Kaifu Gao 1,  Rui Wang 1,  Jiahui Chen 1,  Jetze J Tepe 2,  Faqing Huang 3,  Guo-Wei Wei 1 4 5
Affiliations

Affiliations

  • 1 Department of Mathematics, Michigan State University, East Lansing, Michigan 48824, United States.
  • 2 Department of Chemistry and Pharmacology & Toxicology, Michigan State University, East Lansing, Michigan 48824, United States.
  • 3 Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, Mississippi 39406, United States.
  • 4 Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, United States.
  • 5 Department of Electrical and Computer Engineering, Michigan State University, East Lansing, Michigan 48824, United States.
PMID: 34798775 DOI: 10.1021/acs.jmedchem.1c00409
Abstract

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

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