The investigator plans to determine the feasibility of using glucosidase inhibitors as anti-hepatitis B and C virus agents. These phase I studies will determine if alpha-glucosidase inhibitors are effective in preventing the release and spread of lamivudine (3TC)-resistant mutants of HBV in cell culture. Studies to examine the frequency of spontaneously occurring glucosidase inhibitor mutants of bovine viral diarrhea virus, which will be used as a tissue culture model for HCV will also be performed. If such mutants arise, they will then be isolated and characterized. Future phase II studies will focus on modifying the imino sugar to enhance potency and will perform animal toxicity studies with the lead compound. Experiments to examine the efficacy of glucosidase inhibitors against 3TC-resistant mutants of woodchuck hepatitis virus in animals will also be expanded in the phase II studies.
NOT AVAILABLE
| Ouzounov, Serguey; Mehta, Anand; Dwek, Raymond A et al. (2002) The combination of interferon alpha-2b and n-butyl deoxynojirimycin has a greater than additive antiviral effect upon production of infectious bovine viral diarrhea virus (BVDV) in vitro: implications for hepatitis C virus (HCV) therapy. Antiviral Res 55:425-35 |
| Jordan, Robert; Nikolaeva, Olga V; Wang, Lijuan et al. (2002) Inhibition of host ER glucosidase activity prevents Golgi processing of virion-associated bovine viral diarrhea virus E2 glycoproteins and reduces infectivity of secreted virions. Virology 295:10-9 |
