Inhibition of Bovine Viral Diarrhea Virus (BVDV) by Mizoribine: Synergistic Effect of Combination with Interferon-alpha

Bovine viral diarrhea virus (BVDV) is a well-characterized member of the Flaviviridae family. BVDV may be a surrogate model for human hepatitis C virus (HCV), since HCV does not replicate efficiently in cell cultures and animals. Mizoribine, a nucleoside analog clinically used as an immunosuppressant, was found to be active against the replication of BVDV in cell culture. We further investigated the combination of mizoribine and interferon (IFN)-alpha for antiviral activity and found that the combination synergistically inhibited BVDV replication in bovine kidney cells, as monitored by the inhibition of virus-induced cytopathicity. The combination of ribavirin and IFN-alpha was also synergistic in inhibiting BVDV replication. Treatment of infected cells with a combination of mizoribine and IFN-alpha at the concentrations, at which the respective compounds proved to be inactive, markedly reduced viral infectivity in culture supernatants. These results indicate that mizoribine in combination with IFN-alpha may have potential for the treatment of HCV infection.