Ribavirin (ICN-1229)

Ribavirin significantly reduces the efficiency with which progeny subgenomic replicons transfect new cells in the replicon system, although ribavirin has little effect on levels of HCV replication. Ribavirin increases the mutation frequency of HCV, with the highest rates of mutations being found in the NS5A-encoding region. Ribavirin enhances TH1 while inhibiting T 2 cytokine production by stimulated T cells. ^[1] Ribavirin shows antiviral activity against a variety of RNA viruses and is used in combination with interferon-alpha to treat hepatitis C virus infection. Ribavirin reduces infectious poliovirus production to as little as 0. 00001% in cell culture. ^[2] Ribavirin's antiviral activity is exerted directly through lethal mutagenesis of the viral genetic material. ^[3] Ribavirin markedly reduces viral-induced parameters of macrophage activation at physiologic concentrations (up to 500 mg/mL). Ribavirin inhibits the production of IL-4 by Th2 cells, whereas it does not diminish the production of IFN-gamma in Th1 cells. ^[4] Ribavirin exhibits antiviral activity against a broad range of both DNA and RNA viruses in vitro. Ribavirin is a cytostatic agent and causes a reduction in synthesis of DNA, RNA and proteins in exposed cells. Ribavirin is thought to induce a switch in T-helper cell phenotype from type 2 to type 1. ^[5]