penciclovir and Hepatitis-B

The current arsenal of antiviral agents available to the practitioner is expanding rapidly, such that by the time this article goes to press, new drugs may have already been added. Although the majority of approved drugs have been developed for use in only a few viral infections (eg, HIV, herpesviruses, and papillomavirus), discoveries made in the development of these drugs may lead to antiviral agents effective against other viruses. In addition, new uses for the currently available drugs are under evaluation. This review of antiviral agents discusses the treatments available for viral infections such as herpes simplex virus, varicella zoster virus, cytomegalovirus, human papillomavirus, chronic viral hepatitis, and others.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Famciclovir; Foscarnet; Guanine; Hepatitis B; Hepatitis C; Herpes Genitalis; Herpes Simplex; Herpesvirus 3, Human; Herpesvirus 8, Human; Humans; Papillomavirus Infections; Sarcoma, Kaposi; Skin Diseases, Viral; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Drug Resistance, Viral; Famciclovir; Guanine; Hepatitis B; Hepatitis C; Herpes Simplex; Herpes Zoster; Humans; Influenza, Human; Valacyclovir; Valine; Virus Diseases

Mycophenolic acid [the active metabolite of the immunosuppressive agent mycophenolate mofetil (MMF)] and ribavirin were found to potentiate the anti-HBV activity of the guanine-based nucleoside analogues penciclovir (PCV), lobucavir (LBV) and 3'-fluorodideoxyguanosine (FLG) and diaminopurine dioxolane (DAPD). Ribavirin and mycophenolic acid are both inhibitors of inosine 5'-monophosphate dehydrogenase and cause a depletion of intracellular dGTP levels. It may be assumed that the 5'-triphosphorylated derivatives of the guanine-based nucleoside analogues, in the presence of reduced levels of dGTP, inhibit more efficiently the priming reaction as well as the reverse transcription and DNA-dependent DNA polymerase activity of the HBV polymerase. This assumption is corroborated by the observation that exogenously added guanosine reversed the potentiating effect of ribavirin and mycophenolic acid on the anti-HBV activity of the guanosine analogues. Our observations may have implications for those (liver) transplant recipients that receive MMF as (part of their) immunosuppressive regimen and that, because of de novo or persistent infection with HBV, need specific anti-HBV therapy.

Topics: Acyclovir; Antiviral Agents; Cell Line; Dideoxynucleosides; Dioxolanes; Drug Synergism; Filaggrin Proteins; Guanine; Guanosine; Hepatitis B; Hepatitis B virus; Humans; Mycophenolic Acid; Purine Nucleosides; Ribavirin; Virus Replication

Topics: Acyclovir; Animals; Antiviral Agents; Cells, Cultured; Chronic Disease; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Guanine; Hepatitis B; Hepatitis B Virus, Duck; Humans; Lamivudine; Liver; Virus Replication

The HBV-producing human hepatoblastoma cell line, 2.2.15, has been shown to be an accurate model of chronic cellular viral infection and a predictive model of antiviral response for in vivo hepadnaviral infection. Our laboratory has utilized the 2.2.15 cell line in a standardized assay to examine treatment schemes which use combinations of clinically relevant nucleoside analogues, novel methods to deliver potentially useful nucleoside combinations, and treatments which simultaneously target different parts of the HBV replication pathway. For example, the combination of 3TC (lamivudine) with either alpha interferon or penciclovir significantly enhances the antiviral effectiveness of these agents against HBV replication in 2.2.15 cell culture.

Topics: Acyclovir; Antiviral Agents; Drug Synergism; Drug Therapy, Combination; Guanine; Hepatitis B; Hepatitis B virus; Hepatoblastoma; Humans; Interferon-alpha; Lamivudine; Tumor Cells, Cultured; Virus Replication; Zalcitabine