Remdesivir triphosphate can efficiently inhibit the RNA-dependent RNA polymerase from various flaviviruses

Antiviral Res. 2020 Oct:182:104899. doi: 10.1016/j.antiviral.2020.104899. Epub 2020 Aug 5.

Abstract

Remdesivir was shown to inhibit RNA-dependent RNA-polymerases (RdRp) from distinct viral families such as from Filoviridae (Ebola) and Coronaviridae (SARS-CoV, SARS-CoV-2, MERS). In this study, we tested the ability of remdesivir to inhibit RdRps from the Flaviviridae family. Instead of remdesivir, we used the active species that is produced in cells from remdesivir, the appropriate triphosphate, which could be directly tested in vitro using recombinant flaviviral polymerases. Our results show that remdesivir can efficiently inhibit RdRps from viruses causing severe illnesses such as Yellow fever, West Nile fever, Japanese and Tick-borne encephalitis, Zika and Dengue. Taken together, this study demonstrates that remdesivir or its derivatives have the potential to become a broad-spectrum antiviral agent effective against many RNA viruses.

Keywords: Flavivirus; Inhibitor; RNA-dependent RNA polymerase; Remdesivir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / pharmacology
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Betacoronavirus / drug effects
  • Betacoronavirus / enzymology
  • COVID-19
  • COVID-19 Drug Treatment
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology*
  • Flavivirus / drug effects*
  • Flavivirus / enzymology
  • Humans
  • Inhibitory Concentration 50
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology*
  • RNA Viruses / drug effects
  • RNA Viruses / enzymology
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • RNA-Dependent RNA Polymerase / metabolism
  • SARS-CoV-2

Substances

  • Antiviral Agents
  • Adenosine Triphosphate
  • GS-441524 triphosphate
  • RNA-Dependent RNA Polymerase