Pharmaceuticals (Sep 2021)

Sub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural Compounds

  • Bruno Rizzuti,
  • Laura Ceballos-Laita,
  • David Ortega-Alarcon,
  • Ana Jimenez-Alesanco,
  • Sonia Vega,
  • Fedora Grande,
  • Filomena Conforti,
  • Olga Abian,
  • Adrian Velazquez-Campoy

DOI
https://doi.org/10.3390/ph14090892
Journal volume & issue
Vol. 14, no. 9
p. 892

Abstract

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Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main protease, with an inhibition constant in the sub-micromolar range (Ki = 0.81 μM). Two phenylpropene analogs were also tested: the same effect was observed for estragole with a lower potency (Ki = 4.1 μM), whereas anethole was less active. The binding efficiency index of these compounds is remarkably favorable due also to their small molecular mass (MW < 165 Da). We envision that nanomolar inhibition of 3CLpro is widely accessible within the chemical space of simple natural compounds.

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