Applied Sciences (Jul 2021)

Mechanistic Insight into SARS-CoV-2 M<sup>pro</sup> Inhibition by Organoselenides: The Ebselen Case Study

  • Andrea Madabeni,
  • Pablo Andrei Nogara,
  • Folorunsho Bright Omage,
  • João Batista Teixeira Rocha,
  • Laura Orian

DOI
https://doi.org/10.3390/app11146291
Journal volume & issue
Vol. 11, no. 14
p. 6291

Abstract

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The main protease (Mpro) of SARS-CoV-2 is a current target for the inhibition of viral replication. Through a combined Docking and Density Functional Theory (DFT) approach, we investigated in-silico the molecular mechanism by which ebselen (IUPAC: 2-phenyl-1,2-benzoselenazol-3-one), the most famous and pharmacologically active organoselenide, inhibits Mpro. For the first time, we report on a mechanistic investigation in an enzyme for the formation of the covalent -S-Se- bond between ebselen and a key enzymatic cysteine. The results highlight the strengths and weaknesses of ebselen and provide hints for a rational drug design of bioorganic selenium-based inhibitors.

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