RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic

Eur J Med Chem. 2021 Mar 5:213:113201. doi: 10.1016/j.ejmech.2021.113201. Epub 2021 Jan 21.

Abstract

The widespread nature of several viruses is greatly credited to their rapidly altering RNA genomes that enable the infection to persist despite challenges presented by host cells. Within the RNA genome of infections is RNA-dependent RNA polymerase (RdRp), which is an essential enzyme that helps in RNA synthesis by catalysing the RNA template-dependent development of phosphodiester bonds. Therefore, RdRp is an important therapeutic target in RNA virus-caused diseases, including SARS-CoV-2. In this review, we describe the promising RdRp inhibitors that have been launched or are currently in clinical studies for the treatment of RNA virus infections. Structurally, nucleoside inhibitors (NIs) bind to the RdRp protein at the enzyme active site, and nonnucleoside inhibitors (NNIs) bind to the RdRp protein at allosteric sites. By reviewing these inhibitors, more precise guidelines for the development of more promising anti-RNA virus drugs should be set, and due to the current health emergency, they will eventually be used for COVID-19 treatment.

Keywords: COVID-19; Nucleoside/non-nucleoside analogue inhibitor; RNA virus; RNA-dependent RNA polymerase (RdRp); SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / therapeutic use*
  • COVID-19 / epidemiology
  • COVID-19 Drug Treatment*
  • Coronavirus RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Drug Repositioning*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Nucleosides / chemistry
  • Nucleosides / therapeutic use
  • Pandemics
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / enzymology

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Nucleosides
  • Coronavirus RNA-Dependent RNA Polymerase
  • NSP12 protein, SARS-CoV-2