Inhibition of human and duck hepatitis B virus by 2',3'-dideoxy-3'-fluoroguanosine in vitro.
The fluorinated guanosine analog 2',3'-dideoxy-3'-fluoroguanosine (FLG) has been shown to have an effect on duck hepatitis B virus (DHBV) in vivo and in vitro. In this study the inhibitory effect of FLG on DHBV and human hepatitis B virus (HBV) was evaluated in vitro. Cell lines transfected either with DHBV or HBV DNA and primary duck hepatocyte cell cultures were used. Virus production was analysed by PCR and a quantitative PCR was established for DHBV for determination of the inhibitory concentrations of the drug. 50% inhibition was achieved with an FLG concentration of 0.2 microg/ml (0.7 microM) and 90% inhibition was observed with an FLG concentration of 1.0 microg/ml (3.7 microM) using the DHBV transfected cell line. FLG showed an effect on DHBV production in primary duck hepatocyte cell cultures at concentrations down to 0.1 microg/ml (0.4 microM). However, the DHBV production returned to pre-treatment levels within a few days after cessation of treatment. HBV production in transfected cell lines was also inhibited by FLG. Both DHBV and HBV DNA-polymerases were inhibited by FLG triphosphate and 50% inhibition was observed at a concentration of 0.05 microg/ml (0.1 microM) for DHBV and 0.03 microg/ml (0.05 microM) for HBV. FLG is an efficient inhibitor of DHBV replication both in vivo and in vitro and of HBV in vitro which makes it a good candidate for treatment of HBV infections. However, it does not completely eliminate the virus since a relapse in virus production was observed when treatment was withdrawn. Therefore it would be interesting to evaluate FLG in combination with other types of anti-HBV drugs.
Schröder
I
I
Department of Medical Microbiology, University of Lund, Sweden.
Holmgren
B
B
Oberg
M
M
Löfgren
B
B
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D002478:Cells, Cultured; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004372:Ducks; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000091344:Filaggrin Proteins; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000821:virology; D019384:Nucleic Acid Synthesis Inhibitors; D016133:Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015224:Dideoxynucleosides; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D019384:Nucleic Acid Synthesis Inhibitors; C055315:3'-fluoro-2',3'-dideoxyguanosine