Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor

Bioorg Med Chem Lett. 2005 Dec 15;15(24):5365-9. doi: 10.1016/j.bmcl.2005.09.012. Epub 2005 Oct 10.

Abstract

The coronavirus main protease, M(pro), is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to identify potential M(pro) inhibitors. The data revealed that the coronaviral main protease is inhibited by aziridine- and oxirane-2-carboxylates. Among the trans-configured aziridine-2,3-dicarboxylates the Gly-Gly-containing peptide 2c was found to be the most potent inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aziridines / pharmacology*
  • Binding Sites
  • Coronavirus 3C Proteases
  • Cysteine Endopeptidases / metabolism
  • Humans
  • Peptides / pharmacology*
  • Protease Inhibitors / pharmacology*
  • Severe Acute Respiratory Syndrome / drug therapy*
  • Severe acute respiratory syndrome-related coronavirus / drug effects
  • Viral Proteins / metabolism

Substances

  • Aziridines
  • Peptides
  • Protease Inhibitors
  • Viral Proteins
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases