Structure-Activity Studies Reveal Scope for Optimisation of Ebselen-Type Inhibition of SARS-CoV-2 Main Protease

ChemMedChem. 2022 Feb 16;17(4):e202100582. doi: 10.1002/cmdc.202100582. Epub 2021 Dec 27.

Abstract

The reactive organoselenium compound ebselen is being investigated for treatment of coronavirus disease 2019 (COVID-19) and other diseases. We report structure-activity studies on sulfur analogues of ebselen with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro ), employing turnover and protein-observed mass spectrometry-based assays. The results reveal scope for optimisation of ebselen/ebselen derivative- mediated inhibition of Mpro , particularly with respect to improved selectivity.

Keywords: COVID-19; Mpro inhibition; SARS-CoV-2; ebselen; ebsulfur; nucleophilic cysteine protease..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / virology
  • Coronavirus 3C Proteases / antagonists & inhibitors*
  • Humans
  • Isoindoles / chemistry
  • Isoindoles / pharmacology*
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • SARS-CoV-2 / enzymology*
  • Structure-Activity Relationship

Substances

  • Isoindoles
  • Organoselenium Compounds
  • Protease Inhibitors
  • ebselen
  • 3C-like proteinase, SARS-CoV-2
  • Coronavirus 3C Proteases