Top-hits for H1N1pdm identified by virtual screening using ensemble-based docking

Abstract

A list of 27 promising antiviral drugs is proposed for use against the H1N1pdm strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of the bird flu H5N1, an effective means to quickly identify top candidates for use against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI diversity set which bind best to H5N1 neuraminidase. These compounds serve as viable candidates for docking against the H1N1pdm neuraminidase, using ensembles extracted from molecular dynamics simulations of the H1N1pdm system. The ranking order of these top candidates was found to be different from the previously published results for H5N1. The results indicated that the Oseltamivir (Tamiflu) and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six drug candidates were found to bind more effectively to H1N1pdm neuraminidase than Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also provided.