New Potent Antiviral Against Cytomegalovirus

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It revealed pharmacophore features adding optimal antiviral profile, including the 5-OH, the N-1 benzyl, at least one -CH2− in the linker, and a di-halogen substituted phenyl ring in the amide moiety.

Various analogs were found with sub-micromolar antiviral potency and good selectivity index. The preliminary mechanism of action characterization used a pUL89-C biochemical endonuclease assay, a virus entry assay, a time-of-addition assay, and a compound withdrawal assay.

ADME profiling measuring aqueous solubility, plasma and liver microsomal stability, and parallel artificial membrane permeability assay (PAMPA) permeability demonstrated largely favorable drug-like properties.

These studies validate the N-benzyl hydroxypyridone carboxamide as a viable chemotype for potent and mechanistically distinct antivirals against HCMV.

Source: Medindia



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