Prediction of selective inhibition of neuraminidase from various influenza virus strains by potential inhibitors

Abstract

A universal model of inhibition of neuraminidases from various influenza virus strains by a particular inhibitor has been developed. It is based on known 3D structures for neuraminidases from three influenza virus strains (A/Tokyo/3/67, A/tern/Australia/G70C/75, B/Lee/40) and modeling of the 3D structure of neuraminidases from other strains (A/PR/8/34 and A/Aichi/2/68). Using docking and molecular dynamics, we have modeled 235 enzyme-ligand complexes for 185 compounds with known IC₅₀ values. Selection of final variants among three intermediate results obtained for each enzyme-ligand pair and calculation of independent variables for generation of linear regression equations were performed using MM-PBSA/MM-GBSA. This resulted in the set of equations for individual strains and the equations pooling all the data. Thus using this approach it is possible to predict inhibition for neuraminidase from each the considered strains by a particular inhibitor and to predict the range of its action on neuraminidases from various influenza virus strains.