Antiviral strategies in chronic hepatitis B virus infection: II. Inhibition of duck hepatitis B virus in vitro using conventional antiviral agents and supercoiled-DNA active compounds.
Primary duck hepatocyte (PDH) cultures, congenitally infected with the duck hepatitis B virus (DHBV), were grown on feeder cell layers of irradiated human embryonic lung fibroblasts and then exposed to a number of compounds with recognized or potential antiviral activity. These compounds included conventional antiviral agents, reverse transcriptase inhibitors, compounds with activity to supercoiled-DNA, and DNA-binding agents. Twenty-three compounds were evaluated, and 13 were found to inhibit significantly viral DNA replication. Seven of these compounds (ellipticine, amsacrine, coumermycin A1, Adriamycin, mitozantrone, chloroquine, and neocarzinostatin) acted at the level of viral SC DNA and significantly inhibited production of duck hepatitis B surface antigen (DHBsAg). Conventional agents that inhibited DHBV DNA replication included ganciclovir, acyclovir, bromovinyldeoxyuridine, ribavirin, phosphonoformate, and dideoxyadenosine. Except for dideoxyadenosine, these inhibitors of viral DNA synthesis did not significantly inhibit DHBsAg production. Two additional compounds, novobiocin and nalidixic acid, altered the pattern of viral DNA replication, especially the generation and processing of viral SC DNA, and also inhibited the production of DHBsAg. Several compounds acting at the level of viral SC DNA have now been identified and may offer potential for the management of chronic hepatitis B virus infection.
Hepatitis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield Hospital, Victoria, Australia.
G
G
Civitico
Y Y
YY
Wang
C
C
Luscombe
N
N
Bishop
G
G
Tachedjian
I
I
Gust
S
S
Locarnini
D000818:Animals; D000998:Antiviral Agents / Q000145:classification / Q000494:pharmacology*; D002478:Cells, Cultured; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D004278:DNA, Superhelical / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004372:Ducks; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006524:Hepatitis, Viral, Animal / Q000473:pathology*; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004278:DNA, Superhelical; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D007364:Intercalating Agents; D018894:Reverse Transcriptase Inhibitors