HCMV

Maribavir is a potent inhibitor of the autophosporylation of the wild type and all the major Ganciclovir (GCV) resistant UL97 mutants analysed with a mean IC ₅₀ of 35 nM. The M460I mutation results in hypersensitivity to Maribavir with an IC ₅₀ of 4.8 nM. A Maribavir resistant mutant of UL97 (L397R) is functionally compromised as both a Ganciclovir kinase and a protein kinase (~ 10% of wild type levels). Enzyme kinetic experiments demonstrate that Maribavir is a competitive inhibitor of ATP with a K _i of 10 nM. Maribavir (1263W94) inhibits viral replication in a dose-dependent manner, with IC ₅₀ of 0.12±0.01 μM as measured by a multicycle DNA hybridization assay. The pUL97 protein kinase is strongly inhibited by Maribavir, with 50% inhibition occurring at 3 nM.