The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen

Nat Med. 2000 Dec;6(12):1375-9. doi: 10.1038/82191.

Abstract

The ribonucleoside analog ribavirin (1-beta-D-ribofuranosyl-1,2, 4-triazole-3-carboxamide) shows antiviral activity against a variety of RNA viruses and is used in combination with interferon-alpha to treat hepatitis C virus infection. Here we show in vitro use of ribavirin triphosphate by a model viral RNA polymerase, poliovirus 3Dpol. Ribavirin incorporation is mutagenic, as it templates incorporation of cytidine and uridine with equal efficiency. Ribavirin reduces infectious poliovirus production to as little as 0. 00001% in cell culture. The antiviral activity of ribavirin correlates directly with its mutagenic activity. These data indicate that ribavirin forces the virus into 'error catastrophe'. Thus, mutagenic ribonucleosides may represent an important class of anti-RNA virus agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / pharmacology*
  • DNA-Directed RNA Polymerases / drug effects
  • Mutagens / pharmacology*
  • Nucleotides / pharmacology*
  • Poliovirus / drug effects
  • Protein Biosynthesis / drug effects
  • RNA Replicase*
  • RNA Viruses / drug effects*
  • Ribavirin / analogs & derivatives*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Mutagens
  • Nucleotides
  • Ribavirin
  • ribavirin 5'-triphosphate
  • polymerase 3Dpol, poliovirus
  • RNA Replicase
  • DNA-Directed RNA Polymerases