Systematic Search for SARS-CoV-2 Main Protease Inhibitors for Drug Repurposing: Ethacrynic Acid as a Potential Drug

Viruses. 2021 Jan 13;13(1):106. doi: 10.3390/v13010106.

Abstract

In 2019 an outbreak occurred which resulted in a global pandemic. The causative agent has been identified in a virus belonging to theCoronaviridae family, similar to the agent of SARS, referred to as SARS-CoV-2. This epidemic spread rapidly globally with high morbidity and mortality. Although vaccine development is at a very advanced stage, there are currently no truly effective antiviral drugs to treat SARS-CoV-2 infection. In this study we present systematic and integrative antiviral drug repurposing effort aimed at identifying, among the drugs already authorized for clinical use, some active inhibitors of the SARS-CoV-2 main protease. The most important result of this analysis is the demonstration that ethacrynic acid, a powerful diuretic, is revealed to be an effective inhibitor of SARS-CoV-2 main protease. Even with all the necessary cautions, given the particular nature of this drug, these data can be the starting point for the development of an effective therapeutic strategy against SARS-CoV-2.

Keywords: 3C-like protease; 3CL protease; COVID-19; Mpro; SARS-CoV-2; coronavirus; drug repurposing; main protease; protease inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Catalytic Domain
  • Coronavirus 3C Proteases / antagonists & inhibitors*
  • Coronavirus 3C Proteases / chemistry
  • Coronavirus 3C Proteases / metabolism
  • Databases, Factual
  • Drug Repositioning
  • Ethacrynic Acid / chemistry
  • Ethacrynic Acid / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacokinetics*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / enzymology

Substances

  • Antiviral Agents
  • Protease Inhibitors
  • Coronavirus 3C Proteases
  • Ethacrynic Acid