In-silico Drug Design and In-silico Screening (Track)

Mutational patterns in Avian and Swine flu viruses and identification of surface exposed conserved region in neuraminidase and VP7 proteins by graphical representation and numerical characterization (GRANCH) studies

Ashesh Nandy
Centre for Interdisciplinary Research and Education, Jodhpur Park, Kolkata 700068, India


Abstract:

All major biological phenomena have their roots in the DNA sequence where alterations can lead to major changes of evolutionary significance. Study of mutational changes in the highly pathogenic H5N1 and H1N1 flu virus DNA and protein sequences is therefore of great importance to understand their variability and evolutionary consequences. It is especially important to understand the changes in the neuraminidase gene sequence of this virus since it is of primary importance in the infection of the host cells and elution of generated virions and is also the target of the only drugs we have at this time to treat this form of influenza in human beings. Our study focused on viral phenomena like strain development, viral mutability, viral recombination frequencies etc. which may lead to understanding of the evolution of this virus and the continuation of the applicability of the current forms of the drugs and have shown many important results. We applied graphical representation and numerical characterization techniques on H5N1’s neuraminidase database to quantify the genomic phenomena and informations. Our analysis covering 682 complete H5N1 neuraminidase genes and protein sequence available in the database updated to March 2009 have confirmed that full sequences and their structural segments appeared over significant distances in space and time, indicating need for a deeper understanding of the longevity of such viral strains in the environment. Numerical representation and graphical analysis on the viral structural segments have shown existence of a trend for segmentwise recombination for which we have proposed a model of recombination taking structural segment as the recombination unit. A 50-base c-terminal tail section identified in our earlier paper is seen to be highly conserved and appears to accumulate mutational changes at a rate of about a fifth to an eighth of transmembrane and stalk regions, although the length is about half of these. Our analysis of conserved and surface exposed regions from the 3D structure of the neuraminidase protein also identified six conserved patches on NA protein surface which can be of immense importance for their biological role and as potential targets for new drugs against this form of influenza. An application of this technique to the rotavirus VP7 was also able to identify several such regions indicating the usefulness of this method to design of new drugs and vaccines.