Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1996-7-25
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
941-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Inhibition of Epstein-Barr virus replication by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil.
pubmed:affiliation
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.