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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1996-12-10
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pubmed:abstractText |
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 Short-term therapy could not prevent a rebound of viral replication after the drug was withdrawn.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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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-1321132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-1384989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-1629711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-1656445,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-1718087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-2195346,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-2335817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-2466368,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-2474480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-2477299,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-2545588,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-2647612,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-2729928,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-2745424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-3038725,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-3512855,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-6165830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-7504742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-7515609,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-7518218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-7525990,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-7966625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-7989703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-8145230,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-8289335,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-8294097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8834896-8304960
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0066-4804
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
448-53
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8834896-Animals,
pubmed-meshheading:8834896-Antiviral Agents,
pubmed-meshheading:8834896-Blotting, Southern,
pubmed-meshheading:8834896-Cells, Cultured,
pubmed-meshheading:8834896-DNA, Viral,
pubmed-meshheading:8834896-DNA Replication,
pubmed-meshheading:8834896-Ducks,
pubmed-meshheading:8834896-Female,
pubmed-meshheading:8834896-Hepadnaviridae Infections,
pubmed-meshheading:8834896-Hepatitis B Virus, Duck,
pubmed-meshheading:8834896-Liver,
pubmed-meshheading:8834896-Reverse Transcriptase Inhibitors,
pubmed-meshheading:8834896-Time Factors,
pubmed-meshheading:8834896-Virus Replication,
pubmed-meshheading:8834896-Zalcitabine
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pubmed:year |
1996
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pubmed:articleTitle |
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.
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pubmed:affiliation |
INSERM U271, Lyon, France.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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