Protein homology modeling and structure-function relationship of 2009 swine influenza virus hemagglutinin (HA1): more human than swine

Abstract

The virulence and transmissibility of viruses are highly associated with their binding specificity to the host cell receptor. In influenza, this initial event of viral pathogenesis is mediated by a glycoprotein known as hemagglutinin (HA). In the present study we constructed homology models of the chain A of hemagglutinin (HA1) of 2009 swine influenza strain. The modeled proteins were compared with atomic coordinates of 1918 (Spanish flu strain) and 1930 HA1 (swine influenza strain). HA1 of recent swine influenza strain showed 84.83% and 93.14% homology with the same versions of 1918 and 1930 strains, respectively. Discrepancies in multiple sequence alignment particularly at the ligand-binding residues notified its receptor specificity to α-2,6 sialic acids in 1918 and 2009 viral strains in contrast to α-2,3 sialic acids as found in 1930 swine flu strain. This implicated the relatively closer relationship of 2009 strain with 1918 strain rather than swine origin strain of 1930. Similarly, the spatial orientations of receptor-binding residues, located in 190-helix, 130-loop and 220-loop, were found more aligned in 1918 and 2009 (RMSD 0.98 Å) than in 1930 and 2009 (RMSD 1.06 Å) strains HA1. More similarities were established between both human origin influenza viruses (1918 and 2009 strains) by the receptor-binding cavity architecture and the orientation of protease cleavage site (Arg327). Briefly, the present finding is expected to show molecular discrepancies and congruencies among the recent and past pandemic influenza strains and may also potentially illustrate the drug targets to rein the infection at earlier stages.