2',3'-dideoxy-3'-fluoroguanosine inhibits duck hepatitis B virus in vivo.
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, 5 mg 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.
Löfgren
B
B
Department of Medical Microbiology, Lund University, Sweden.
Vickery
K
K
Zhang
Y Y
YY
Nordenfelt
E
E
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001715:Bird Diseases; D004279:DNA, Viral / Q000096:biosynthesis*; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004372:Ducks; D000091344:Filaggrin Proteins; D005461:Fluorine / Q000494:pharmacology; D006509:Hepatitis B / Q000188:drug therapy / Q000662:veterinary*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification*
D000998:Antiviral Agents; D004279:DNA, Viral; D015224:Dideoxynucleosides; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D005461:Fluorine