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 ce ll cultures were used. Virus production was analysed by PCR and a quan titative PCR was established for DHBV for determination of the inhibit ory concentrations of the drug. 50% inhibition was achieved with an FL G concentration of 0.2 mu g/ml (0.7 mu M) and 90%, inhibition was obse rved with an FLG concentration of 1.0 mu g/ml (3.7 mu M) using the DHB V transfected cell line. FLG showed an effect on DHBV production in pr imary duck hepatocyte cell cultures at concentrations down to 0.1 mu g /ml (0.4 mu M). 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 HB V DNA-polymerases were inhibited by FLG triphosphate and 50% inhibitio n was observed at a concentration of 0.05 mu g/ml (0.1 mu M) for DHBV and 0.03 mu g/ml (0.05 mu M) 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it does not completely eliminate the virus since a relapse in virus prod uction was observed when treatment was withdrawn. Therefore it would b e interesting to evaluate FLG in combination with other types of anti- HBV drugs. (C) 1998 Elsevier Science B.V.