Ribavirin may exert its broad-spectrum antiviral activity by causing lethal mutagenesis of the viral genome, mediated by the viral RNA-dependent RNA polymerase.
This review highlights the hypothesis that ribavirin acts via lethal mutagenesis of viral genomes, offering insights into its antiviral efficacy and potential therapeutic strategies.
Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole) is a broad-spectrum antiviral nucleoside that is currently used in combination with interferon-alpha to treat hepatitis C virus infection and as a monotherapy to treat severe cases of respiratory syncytial virus infection and Lassa fever virus infection. The mechanism of action of ribavirin has been studied for decades. These studies have suggested that the antiviral activity of ribavirin may be related to its ability to cause a decrease in intracellular guanosine triphosphate pools, to inhibit capping of viral transcripts or to suppress humoral and cellular immune responses. Last year, another possibility was added to this list. The new proposition is that ribavirin, when converted to the triphosphate, is utilized by the viral RNA-dependent RNA polymerase and causes lethal mutagenesis of the viral genome. In this article, the data supporting this new hypothesis are reviewed. We discuss the implications of these data on alternative explanations for the apparent failure of ribavirin monotherapy in the treatment of hepatitis C virus infection, connections between developmental defects induced by ribavirin and posttranscriptional gene silencing/RNA interference, and the use of lethal mutagenesis and related concepts as strategies for antiviral therapy.
Cameron et al. (2001) conducted a review in RNA virus infections (e.g., hepatitis C, respiratory syncytial virus, Lassa fever). Ribavirin was evaluated. Ribavirin may exert its broad-spectrum antiviral activity by causing lethal mutagenesis of the viral genome, mediated by the viral RNA-dependent RNA polymerase.