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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1996-7-25
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pubmed:abstractText |
A novel L-nucleoside analog, 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU), was found to be a potent and selective inhibitor of Epstein-Barr virus (EBV) replication. The decrease in the amount of viral production was concentration dependent with a 90% inhibitory concentration of approximately 5 muM. Upon removal of the drug from treated cells, virus production resumed in 21 days. Metabolism studies indicated that L-FMAU could be converted to its mono-,di- and triphosphate metabolites in both EBV producing and non-producing cells than in EBV non-producing cells. The mechanism of selectivity of L-FMAU against EBV producing cells. However, the amount of L-FMAU nucleotides formed was three times larger in EBV producing cells than in EBV non-producing cells. The mechanism of selectivity of L-FMAU against EBV does not appear to be due solely to the preferential phosphorylation of L-FMAU in EBV producing cells. The triphosphate of L-FMAU could not be utilized as a substrate by EBV DNA polymerase or the human DNA polymerases alpha, beta, gamma, or delta. Therefore, the incorporation of L-FMAU residues into viral DNA may not be the mechanism of antiviral activity. This compound appears to have a mechanism of action different from that of any other antiherpes virus nucleoside analogs. In addition, L-FMAU has very low cytotoxicity with 50% inhibition of cell growth occurring at a concentration of 1mM. Given the potent inhibitory activity of this compound against EBV and its inability to be incorporated into cellular DNA, L-FMAU analogs should be explored as a new class of anti-EBV agents.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
941-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8651944-Arabinofuranosyluracil,
pubmed-meshheading:8651944-Autoradiography,
pubmed-meshheading:8651944-Base Sequence,
pubmed-meshheading:8651944-Cells, Cultured,
pubmed-meshheading:8651944-DNA,
pubmed-meshheading:8651944-Herpesvirus 4, Human,
pubmed-meshheading:8651944-Humans,
pubmed-meshheading:8651944-Molecular Sequence Data,
pubmed-meshheading:8651944-Virus Replication
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pubmed:year |
1996
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pubmed:articleTitle |
Inhibition of Epstein-Barr virus replication by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil.
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pubmed:affiliation |
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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