Molecular modeling pharmacophore mapping and design of h1n1 receptor antagonists

Abstract

newline Influenza is a contagious disease instigated by RNA viruses belongs to the family Orthomyxoviridae. The recent influenza H1N1 viral stain has appeared by the genetic combination of three genes i.e. from human, pig and birdand#8223;s H1N1 virus where pig acts as the mixing vessel. The influenza virus structure is unevenly spherical and is enveloped by a lipid membrane. Inside the lipid membrane, mainly there are two types of glycoproteins i.e. hemagglutinin (HA) which facilitates the entry of the virus by attachment of the viral particle and the host cell surface. Another one, neuraminidase (NA) that is responsible for beginning of viral infection by releasing the virions. In this context, we have developed molecular models for both the hemagglutinin and neuraminidase proteins of H1N1 strains from the eastern India region. Then we docked B-Sialic acid and O-Sialic acid in the optimized and energy minimized models of hemagglutinin which reveals crucial H-bond interactions with residues like ALA142, ASP230, GLN231, GLU232 and THR141. Similarly docking of Oseltamivir on the modelled structure of neuraminidase revealed important electrostatic interaction with ARG109, ARG13 and GLU 219 residues. This information may be utilized for both the structure based strategy and the pharmacophore based drug designing. Further, ADME properties of the docked molecule (Oseltamivir) also have been calculated (Human Oral Absorption (HOA) and % HOA) because this has been topic of discussion for long. newlineThe Swine influenza a respiratory disease, which is highly contagious, caused