Key result
Ribavirin acts as an RNA virus mutagen, inducing error catastrophe and drastically reducing viral infectivity, representing a novel mode of action for its antiviral activity.
Ribavirin acts as a mutagen on RNA viruses, representing a novel mode of action that suggests it should be classified into a new antiviral drug class.
Caution against extrapolating in vitro synergy to patients; leaves open clinical efficacy of ribavirin-IFN combinations.
Ribavirin (Rebetol) is an antiviral agent used in combination with interferon alpha-2b (IFN alpha-2b) for the treatment of chronic hepatitis C. Ribavirin has been reported to have a broad-spectrum antiviral activity mainly against RNA viruses. The effect of ribavirin was potentiated when administered in combination with IFN alpha-2b in an antiviral assay using bovine viral diarrhea virus as a surrogate for hepatitis C virus (HCV). Inhibition of host inosine monophosphate dehydrogenase and inhibition of RNA-dependent RNA polymerase (RdRp) of RNA viruses have been reported as the modes of action of ribavirin. Recently, ribavirin has been shown to induce mutation as template for newly generated RNA after uptake in RNA by RdRp of poliovirus, which is an RNA virus as in the case of HCV. It has also been shown that the infectivity of viruses is drastically reduced by the very slight increase in mutations induced by ribavirin. This effect as a mutagen on RNA viruses is a novel mode of ribavirin, and it is thought necessary to classify ribavirin into a new antiviral drug class.
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Ogawa et al. (2002) conducted a review in Chronic hepatitis C. Ribavirin was evaluated. Ribavirin acts as an RNA virus mutagen, inducing error catastrophe and drastically reducing viral infectivity, representing a novel mode of action for its antiviral activity.
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