Synthesis and biological evaluation of novel peptidomimetic inhibitors of the coronavirus 3C-like protease

Eur J Med Chem. 2024 Mar 15:268:116263. doi: 10.1016/j.ejmech.2024.116263. Epub 2024 Feb 24.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and related variants, are responsible for the devastating coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 main protease (Mpro) plays a central role in the replication of the virus and represents an attractive drug target. Herein, we report the discovery of novel SARS-CoV-2 Mpro covalent inhibitors, including highly effective compound NIP-22c which displays high potency against several key variants and clinically relevant nirmatrelvir Mpro E166V mutants.

Keywords: 3CL(pro); Antivirals; HCoV-OC43; Main protease; Mpro; NIP-22c; Peptides; SARS-CoV-2.

MeSH terms

  • Antiviral Agents / pharmacology
  • COVID-19*
  • Cysteine Endopeptidases
  • Humans
  • Peptide Hydrolases
  • Peptidomimetics* / pharmacology
  • Protease Inhibitors / pharmacology
  • SARS-CoV-2

Substances

  • Peptidomimetics
  • Peptide Hydrolases
  • Protease Inhibitors
  • Cysteine Endopeptidases
  • Antiviral Agents