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.
Yanagida
Koichiro
K
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Baba
Chiaki
C
Baba
Masanori
M
D000818:Animals; D002417:Cattle; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D012254:Ribavirin / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D012263:Ribonucleosides; D012254:Ribavirin; C010052:mizoribine