摘要：

A novel l -nucleoside analog, 2′-fluoro-5-methyl-β- 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 μM. 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. 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 α, β, γ, or δ. 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 1 mM. 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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