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2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo.

Publication ,  Journal Article
Zoulim, F; Dannaoui, E; Borel, C; Hantz, O; Lin, TS; Liu, SH; Trépo, C; Cheng, YC
Published in: Antimicrob Agents Chemother
February 1996

beta-L-Nucleoside analogs represent a new class of potent antiviral agents with low cytotoxicity which provide new hope in the therapy of chronic hepatitis B virus (HBV) infections. We evaluated the anti-HBV activity of 2',3'-dideoxy-beta-L-5-fluorocytidine (beta-L-F-ddC), a beta-L-nucleoside analog derived from 2',3'-dideoxycytidine (ddC), in the duck HBV (DHBV) model. This compound was previously shown to inhibit HBV DNA synthesis in a stably transfected hepatoma cell line (F2215). Using a cell-free system for the expression of an enzymatically active DHBV polymerase, we could demonstrate that the triphosphate form of beta-L-F-ddC does inhibit hepadnavirus reverse transcription. In primary duck hepatocyte culture, beta-L-F-ddC showed a potent inhibitory effect on DHBV DNA synthesis which was concentration dependent. Although beta-L-F-ddC was shown to be less active than ddC against the DHBV reverse transcriptase in vitro, beta-L-F-ddC was a stronger inhibitor in hepatocytes. The oral administration of beta-L-F-ddC in experimentally infected ducklings showed that beta-L-F-ddC is a potent inhibitor of viral replication in vivo. Short-term therapy could not prevent a rebound of viral replication after the drug was withdrawn. Preventive therapy with beta-L-F-ddC could delay the onset of viremia by only 1 day compared with the time to the onset of viremia in the control group. The in vivo inhibitory effect of beta-L-F-ddC was much stronger than that of ddC and was not associated with signs of toxicity. Our data show that beta-L-F-ddC inhibits hepadnavirus reverse transcription and is a strong inhibitor of viral replication both in vitro and in vivo.

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Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

February 1996

Volume

40

Issue

2

Start / End Page

448 / 453

Location

United States

Related Subject Headings

  • Zalcitabine
  • Virus Replication
  • Time Factors
  • Reverse Transcriptase Inhibitors
  • Microbiology
  • Liver
  • Hepatitis B Virus, Duck
  • Hepadnaviridae Infections
  • Female
  • Ducks
 

Citation

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Zoulim, F., Dannaoui, E., Borel, C., Hantz, O., Lin, T. S., Liu, S. H., … Cheng, Y. C. (1996). 2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo. Antimicrob Agents Chemother, 40(2), 448–453. https://doi.org/10.1128/AAC.40.2.448
Zoulim, F., E. Dannaoui, C. Borel, O. Hantz, T. S. Lin, S. H. Liu, C. Trépo, and Y. C. Cheng. “2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo.Antimicrob Agents Chemother 40, no. 2 (February 1996): 448–53. https://doi.org/10.1128/AAC.40.2.448.
Zoulim F, Dannaoui E, Borel C, Hantz O, Lin TS, Liu SH, et al. 2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo. Antimicrob Agents Chemother. 1996 Feb;40(2):448–53.
Zoulim, F., et al. “2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo.Antimicrob Agents Chemother, vol. 40, no. 2, Feb. 1996, pp. 448–53. Pubmed, doi:10.1128/AAC.40.2.448.
Zoulim F, Dannaoui E, Borel C, Hantz O, Lin TS, Liu SH, Trépo C, Cheng YC. 2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo. Antimicrob Agents Chemother. 1996 Feb;40(2):448–453.

Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

February 1996

Volume

40

Issue

2

Start / End Page

448 / 453

Location

United States

Related Subject Headings

  • Zalcitabine
  • Virus Replication
  • Time Factors
  • Reverse Transcriptase Inhibitors
  • Microbiology
  • Liver
  • Hepatitis B Virus, Duck
  • Hepadnaviridae Infections
  • Female
  • Ducks