As noted in the main notes, ribavirin is very effective at inhibiting the infectivity of poliovirus in cell culture, yet this virus does not have a methyl guanosine cap and so the usual mechanism invoked for ribavirin cannot apply in this case. Recently Crotty et al. (Nature Medicine 6, 1375-1379, 2000) have shown that  ribavirin triphosphate can be used by the poliovirus polymerase and incorporated with low efficiency into viral RNA. However, incorporation of ribavirin into polio virus RNA does not terminate the extension of the RNA chain and the amounts of RNA produced are near normal. In addition, translation seems unaffected and peak virus production is close to wild type levels. Yet infectious virus production is reduced by more than 99%. The incorporated drug can base pair with either cytidine or uridine and so is likely to produce mutations. The production of defective genomes was shown by a direct mutation assay  in which it was found that mutation frequency was dependent on the dose of the drug. The authors point out that  RNA viruses create  a great amount of viral diversity by mutation and "exist on the threshold of error-catastrophe" such that an increase in mutation rate can kill a virus population. They showed that  each poliovirus genome made in an infected cell after multiple rounds of replication in the absence of the drug contains two mutations in the 7,441 nucleotide genome. With 1mM ribavirin, this is increased to 15 mutations per genome. This increase in mutation frequency probably renders the virus non-infective.

Ribavirin monophosphate also inhibits the enzyme inosine monophosphate dehydrogenase causing a decrease in the concentration of intracellular GTP. This may be the reason for the apparent failure to cap mRNAs in some viruses. The resulting decrease in  GTP levels in the case of poliovirus may potentiate  mutagenic  activity by lowering the concentration of a nucleotide that competes with the drug for incorporation into RNA and thus raising the insertion of the drug itself.