2‘,3’‐dideoxy‐3‘‐fluoroguanosine inhibits duck hepatitis B virus in vivo

SUMMARY. Duck hepatitis B virus (DHBV) belongs to the same virus family as the human hepatitis B virus (HBV). Domestic ducks infected with DHBV can be used as an animal model for chronic hepatitis B virus infection in therapeutic trials. In this study the antiviral effect of the guanosine analogue 2′,3′‐dideoxy‐3′‐fluoroguanosine (FLG) was tried in vivo on chronically DHBV‐infected ducks. The ducks were either congenitally infected, or inoculated with DHBV immediately post‐hatch. FLG was given as intraperitoneal injections twice daily, at different dosages. Serum DHBV levels were determined by DNA dot‐blot hybridization. A strong inhibition of serum DHBV DNA was observed with FLG doses down to 1 mg kg‐1 day‐1. given for 7 to 10 days. With the corresponding thymidine analogue, 2′,3′‐dideoxy‐3′‐fluorothymidine; however, no inhibition was obtained. This difference may be due to different phosphorylation mechanisms. Independently of FLG dose, serum DHBV DNA returned to pretreatment levels within a few days after cessation of therapy. After a long‐term trial (FLG, 5mg kg‐1 day‐1 for 33 days), the same relapse of DHBV production was seen. Thus, FLG is an efficient inhibitor of DHBV replication, and is a candidate for treatment of HBV infections. However, the effect is transient, and therefore combination with other types of anti‐HBV drugs should be considered.