Molecular interactions and inhibition of the SARS-CoV-2 main protease by a thiadiazolidinone derivative

Proteins. 2022 Nov;90(11):1896-1907. doi: 10.1002/prot.26385. Epub 2022 Jun 3.

Abstract

We report molecular interactions and inhibition of the main protease (MPro ) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore the conformational dynamics of MPro via docking protocols and molecular dynamics simulations in all-atom detail. We reveal the local and global dynamics of MPro in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC50 value of 1.39 ± 0.22 μM, which is comparable to other known inhibitors of this enzyme.

Keywords: SARS-CoV-2; docking; main protease; molecular dynamics; thiadiazolidinone.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Azoles / chemistry*
  • COVID-19 Drug Treatment*
  • Coronavirus 3C Proteases
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • SARS-CoV-2*
  • Viral Nonstructural Proteins / chemistry

Substances

  • Antiviral Agents
  • Azoles
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • 3C-like proteinase, SARS-CoV-2
  • Coronavirus 3C Proteases