Inhibition of viral RNA-dependent RNA polymerases with clinically relevant nucleotide analogs

Enzymes. 2021:49:315-354. doi: 10.1016/bs.enz.2021.07.002. Epub 2021 Oct 15.

Abstract

The treatment of viral infections remains challenging, in particular in the face of emerging pathogens. Broad-spectrum antiviral drugs could potentially be used as a first line of defense. The RNA-dependent RNA polymerase (RdRp) of RNA viruses serves as a logical target for drug discovery and development efforts. Herein we discuss compounds that target RdRp of poliovirus, hepatitis C virus, influenza viruses, respiratory syncytial virus, and the growing data on coronaviruses. We focus on nucleotide analogs and mechanisms of action and resistance.

Keywords: Antivirals; Coronavirus; Hepatitis C virus; Influenza virus; Nucleotide analogs; Poliovirus; RNA virus; Respiratory syncytial virus; Viral polymerase inhibitor.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Nucleotides / pharmacology*
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Viral Replicase Complex Proteins / antagonists & inhibitors*
  • Virus Replication
  • Viruses / enzymology*

Substances

  • Antiviral Agents
  • Nucleotides
  • Viral Replicase Complex Proteins
  • RNA-Dependent RNA Polymerase