SUSCEPTIBILITY OF COMMERCIAL NEURAMINIDASE INHIBITORS AGAINST 2013 A/H7N9 INFLUENZA VIRUS: A DOCKING AND MOLECULAR DYNAMICS STUDY

Abstract

The latest influenza A ( H 7 N 9) virus attracted a worldwide attention due to the first report of human infections and the continuing reported cases in China. In this work, homology modeling, docking and molecular dynamics simulations were combined to study the interactions between neuraminidase ( N 9_2013, from novel A/ H 7 N 9 virus) and agents zanamivir, oseltamivir, peramivir. It was found that N 9_2013 protein is structurally close to the template (PDB code: 1F8B), especially the active site. The binding properties of N 9_2013 protein were nearly identical to those of template. As a result, the three available drugs should be still efficacious for the new emerging A ( H 7 N 9) virus. However, the stabilities of docked complexes and binding affinities (Eint) were slightly reduced, in contrast to the corresponding inhibitor-template complexes, with the values of -82.27 (-84.30), -78.84 (-80.28) and -77.52 (-81.94) kcal mol-1, respectively. Besides, R292K mutation might induce the resistance of the novel virus to the commercial inhibitors. Thus, it arouses the need for continuous monitoring of antiviral drug susceptibilities.