Mass spectrometry reveals potential of β-lactams as SARS-CoV-2 Mpro inhibitors

Chem Commun (Camb). 2021 Feb 15;57(12):1430-1433. doi: 10.1039/d0cc06870e.

Abstract

The main viral protease (Mpro) of SARS-CoV-2 is a nucleophilic cysteine hydrolase and a current target for anti-viral chemotherapy. We describe a high-throughput solid phase extraction coupled to mass spectrometry Mpro assay. The results reveal some β-lactams, including penicillin esters, are active site reacting Mpro inhibitors, thus highlighting the potential of acylating agents for Mpro inhibition.

MeSH terms

  • Acylation
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • COVID-19 / virology
  • Catalytic Domain
  • Cysteine Endopeptidases / drug effects*
  • High-Throughput Screening Assays
  • Humans
  • Mass Spectrometry / methods*
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / enzymology
  • beta-Lactams / chemistry
  • beta-Lactams / pharmacology*

Substances

  • Antiviral Agents
  • Protease Inhibitors
  • beta-Lactams
  • Cysteine Endopeptidases