Inhibitory effect of 2'-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck hepatitis B virus replication.

Antimicrobial Agents and Chemotherapy
S Aguesse-GermonFabien Zoulim

Abstract

The antiviral activity of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU), a novel L-nucleoside analog of thymidine known to be an inhibitor of hepatitis B virus (HBV) replication in hepatoma cells (2.2.1.5 cell line), was evaluated in the duck HBV (DHBV) model. Short-term oral administration (5 days) of L-FMAU (40 mg/kg of body weight/day) to experimentally infected ducklings induced a significant decrease in the level of viremia. This antiviral effect was sustained in animals when therapy was prolonged for 8 days. The histological study showed no evidence of liver toxicity in the L-FMAU-treated group. By contrast, microvesicular steatosis was found in the livers of dideoxycytidine-treated animals. L-FMAU administration in primary duck hepatocyte cultures infected with DHBV induced a dose-dependent inhibition of both virion release in culture supernatants and intracellular viral DNA synthesis, without clearance of viral covalently closed circular DNA. By using a cell-free system for the expression of an enzymatically active DHBV reverse transcriptase, it was shown that L-FMAU triphosphate exhibits an inhibitory effect on the incorporation of dAMP in the viral DNA primer. Thus, our data demonstrate that L-FMAU inhibit...Continue Reading

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Citations

May 23, 2003·Antimicrobial Agents and Chemotherapy·Béatrice SeignèresFabien Zoulim
Dec 25, 2002·Antimicrobial Agents and Chemotherapy·Ayman M AbdelhamedHarriet C Isom
Oct 3, 2007·Antiviral Chemistry & Chemotherapy·Mark A FeitelsonRaymond F Schinazi
Dec 21, 2004·Alimentary Pharmacology & Therapeutics·H M YoungerP C Hayes
Jul 23, 2002·Journal of Virology·Ayman M AbdelhamedHarriet C Isom
Nov 18, 2008·Expert Opinion on Investigational Drugs·Tarik AsselahPatrick Marcellin
Jan 5, 2017·Liver International : Official Journal of the International Association for the Study of the Liver·Barbara TestoniFabien Zoulim
Jan 22, 2003·Journal of Gastroenterology and Hepatology·F ZoulimC Trepo
Jul 29, 2003·Expert Opinion on Investigational Drugs·Anneke K RaneyZhi Hong
Jun 30, 2005·Journal of Viral Hepatitis·P MarcellinN Boyer
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Dec 24, 1998·Antiviral Research·P WangC K Chu
Oct 3, 2006·Expert Review of Anti-infective Therapy·Brent E KorbaMichael J Otto
Jan 4, 2001·European Journal of Medicinal Chemistry·G GaubertG Maury
Apr 5, 2001·Current Infectious Disease Reports·Suzane Kioko Ono-NitaMasao Omata
Jan 8, 2004·Journal of Hepatology·Maria Buti, Rafael Esteban
Aug 29, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Béatrice SeignèresFabien Zoulim
Feb 8, 2006·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·M DandriJ Petersen
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Jul 7, 2007·Archives of Medical Research·Margarita PardoVicente Carreño
Sep 4, 2009·Journal of Fluorine Chemistry·Peng LiuChung K Chu

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