S. Crotty, David Maag, J. Arnold
Dec 1, 2000
Citations
29
Influential Citations
810
Citations
Quality indicators
Journal
Nature Medicine
Abstract
The ribonucleoside analog ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) shows antiviral activity against a variety of RNA viruses and is used in combination with interferon-α 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.