Title: Binding mode analysis of anti-influenza drugs in H1N1 (2009) and H5N1 influenza A virus and designing of potential H1N1 inhibitors

Authors: Kh. Dhanachandra Singh; Palani Kirubakaran; Selvaraman Nagamani; Muthusamy Karthikeyan

Addresses: Department of Bioinformatics, Alagappa University, Karaikudi – 630 004, Tamil Nadu, India ' Department of Bioinformatics, Alagappa University, Karaikudi – 630 004, Tamil Nadu, India ' Department of Bioinformatics, Alagappa University, Karaikudi – 630 004, Tamil Nadu, India ' Department of Bioinformatics, Alagappa University, Karaikudi – 630 004, Tamil Nadu, India

Abstract: The main goal of this study is to understand the molecular-level interactions of neuraminidase inhibitor. The molecular docking, molecular dynamics and binding energy calculation analyses were carried out and the results revealed that the 150-cavitiy in the active site may play an important role in binding of drugs. Free energy calculations revealed that electrostatic interaction is more favourable for Oseltamivir interaction with H1N1 and van der Waals interaction is more favourable for H5N1, whereas Zanamivir favours the electrostatic interaction in both the strains (H1N1 and H5N1). Energy-optimised pharmacophore mapping was created using Oseltamivir drug. The pharmacophore model contained two hydrogen-bond acceptor and two hydrogen bond donor sites. Using these pharmacophore features, we screened a compound database to find a potential ligand that could inhibit the H1N1 protein. The current research will pave the way to find potent neuraminidase inhibitors against H1N1 (2009) strain.

Keywords: H1N1 flu virus; H5N1 flu virus; MM/GBSA; Oseltamivir; Zanamivir; van der Waals; binding mode analysis; anti-influenza drugs; influenza A virus; H1N1 inhibitors; molecular interactions; neuraminidase inhibitors; drug design; molecular docking; molecular dynamics; binding energy; electrostatic interaction; pharmacophore mapping; potential ligands.

DOI: 10.1504/IJCBDD.2015.068753

International Journal of Computational Biology and Drug Design, 2015 Vol.8 No.1, pp.1 - 18

Accepted: 31 Dec 2013
Published online: 07 Apr 2015 *

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