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

Shane Crotty, David Maag, Jamie J. Arnold, Weidong Zhong, Johnson Y.N. Lau, Zhi Hong, Raul Andino, Craig E. Cameron

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612 Scopus citations

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 3D(pol). 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.

Original languageEnglish (US)
Pages (from-to)1375-1379
Number of pages5
JournalNature Medicine
Volume6
Issue number12
DOIs
StatePublished - Dec 1 2000

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Crotty, S., Maag, D., Arnold, J. J., Zhong, W., Lau, J. Y. N., Hong, Z., Andino, R., & Cameron, C. E. (2000). The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nature Medicine, 6(12), 1375-1379. https://doi.org/10.1038/82191