Inhibition of duck hepatitis B virus replication in vitro by 2',3'-dideoxy-3'-azidothymidine and related compounds.
We have adopted the in vitro hepatocyte culture system of the duck infected with duck hepatitis B virus (HDBV) to an anti-viral assay system. Using this method, we found that 2',3'-dideoxy-3'-azidothymidine (N3dT) and 2',3'-dideoxy-3'-O-methylthymidine (OMeT) had antiviral effects against DHBV replication in the concentrations of 20-50 mumol/l and 4-40 mumol/l, respectively. The N3dT inhibited the single strand DNA formation (negative strand), which is an intermediate of virus replication. However, the inhibition of single strand DNA synthesis by OMeT was relatively weak. These two compounds may have different mechanisms of DHBV DNA replication inhibition. Two other 3'-substituted pyrimidine analogues tested were very weak inhibitors. Antiviral agents that inhibit the reverse transcriptase activity of the hepadnavirus DNA polymerase could be potential candidates for the chemotherapy of these viruses.
Suzuki
S
S
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Lorne
D
D
Tyrrell
J
J
Saneyoshi
M
M
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004372:Ducks; D015611:Hepatitis B Virus, Duck / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; D015224:Dideoxynucleosides; C076282:2',3'-dideoxy-3'-O-methylthymidine; D015215:Zidovudine