Implications of high RNA virus mutation rates: lethal mutagenesis and the antiviral drug ribavirin.
The antiviral drug ribavirin exhibits strong antiviral activity against a broad range of RNA viruses. This drug is currently used clinically to treat hepatitis C virus infections, respiratory syncytial virus infections, and Lassa fever virus infections. Although ribavirin was discovered in 1972, its mechanism of action has remained unclear until recently. Using poliovirus as an RNA virus model, it was shown that ribavirin is a virus mutagen, and it was proposed that the primary mechanism of action of ribavirin is via lethal mutagenesis of the RNA virus genomes. This represents a novel antiviral mechanism of action and provides a model for the development of new antiviral strategies. In this review we discuss the genetic explanations, evolutionary implications, and drug development opportunities associated with RNA virus mutagenesis.
Crotty
Shane
S
Department of Microbiology and Immunology, University of California, San Francisco 94143, USA. crotty@microbio.emory.edu
Andino
Raul
R
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D005804:Genes, Lethal; D008958:Models, Molecular; D016296:Mutagenesis; D009154:Mutation; D017955:Poliovirus / Q000187:drug effects / Q000235:genetics; D012328:RNA Viruses / Q000187:drug effects* / Q000235:genetics*; D012254:Ribavirin / Q000737:chemistry / Q000494:pharmacology*
D000998:Antiviral Agents; D012254:Ribavirin