2′,3′-Dideoxy-3′-fluoroguanosine inhibits duck hepatitis B virus in vivo

B. Löfgren*, K. Vickery, Y. Y. Zhang, E. Nordenfelt

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)61-65
Number of pages5
JournalJournal of Viral Hepatitis
Volume3
Issue number2
Publication statusPublished - Mar 1996
Externally publishedYes

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Keywords

  • Anti-viral treatment
  • Duck hepatitis B virus
  • Hepatitis B virus
  • Nucleoside analogues

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