| Abstract
| - The binding sites of wild-type avian influenza A H5N1 neuraminidase,as well as those of the Tamiflu (oseltamivir)-resistant H274Y variant,were explored computationally to design inhibitors that target simultaneouslyseveral adjacent binding sites of the open conformation of the virusprotein. The compounds with the best computed free energies of binding,in agreement by two docking methods, consensus scoring, and ligandefficiency values, suggest that mimicking a polysaccharide, β-lactam,and other structures, including known drugs, could be routes for multibindingsite inhibitor design. This new virtual screening method based onconsensus scoring and ligand efficiency indices is introduced, whichallows the combination of pharmacodynamic and pharmacokinetic propertiesinto unique measures.
|
