The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen.
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.
Crotty
S
S
Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0414, USA.
Maag
D
D
Arnold
J J
JJ
Zhong
W
W
Lau
J Y
JY
Hong
Z
Z
Andino
R
R
Cameron
C E
CE
D000998:Antiviral Agents / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000187:drug effects; D009153:Mutagens / Q000494:pharmacology*; D009711:Nucleotides / Q000494:pharmacology*; D017955:Poliovirus / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D012328:RNA Viruses / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase; D012254:Ribavirin / Q000031:analogs & derivatives*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D009153:Mutagens; D009711:Nucleotides; D012254:Ribavirin; C037827:ribavirin 5'-triphosphate; C090443:polymerase 3Dpol, poliovirus; D012324:RNA-Dependent RNA Polymerase; D012321:DNA-Directed RNA Polymerases