Discovery of chebulagic acid and punicalagin as novel allosteric inhibitors of SARS-CoV-2 3CLpro

Antiviral Res. 2021 Jun:190:105075. doi: 10.1016/j.antiviral.2021.105075. Epub 2021 Apr 17.

Abstract

The emerging SARS-CoV-2 infection is the cause of the global COVID-19 pandemic. To date, there are limited therapeutic options available to fight this disease. Here we examined the inhibitory abilities of two broad-spectrum antiviral natural products chebulagic acid (CHLA) and punicalagin (PUG) against SARS-CoV-2 viral replication. Both CHLA and PUG reduced virus-induced plaque formation in Vero-E6 monolayer at noncytotoxic concentrations, by targeting the enzymatic activity of viral 3-chymotrypsin-like cysteine protease (3CLpro) as allosteric regulators. Our study demonstrates the potential use of CHLA and PUG as novel COVID-19 therapies.

Keywords: 3CLpro; Allosteric inhibitor; Chebulagic acid; Punicalagin; SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Site
  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology*
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Chlorocebus aethiops
  • Coronavirus 3C Proteases / antagonists & inhibitors*
  • Coronavirus 3C Proteases / chemistry
  • Coronavirus 3C Proteases / metabolism
  • Drug Discovery
  • Glucosides / chemistry
  • Glucosides / pharmacology*
  • Hydrolyzable Tannins / pharmacology*
  • Molecular Docking Simulation
  • Protease Inhibitors / pharmacology
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / metabolism
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Benzopyrans
  • Glucosides
  • Hydrolyzable Tannins
  • Protease Inhibitors
  • chebulagic acid
  • punicalagin
  • 3C-like protease, SARS coronavirus
  • Coronavirus 3C Proteases