[Novel mode of action of ribavirin (Rebetol), a drug for the treatment of chronic hepatitis C: inducting the mutation of RNA viruses].
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.
Ogawa
Masami
M
Preclinical Research Department, Research & Development Division, Schering-Plough K.K., 2-3-7 Hiranomachi, Chuo-ku, Osaka 541-0046, Japan.
Morisada
Akiko
A
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D009154:Mutation / Q000187:drug effects*; D012328:RNA Viruses / Q000187:drug effects / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin; D007168:IMP Dehydrogenase; C463299:IMPDH1, mouse; D012324:RNA-Dependent RNA Polymerase