Mutations in surface protein of swine flu: A major problem for H1N1 inhibitor

The emergence of new mutant strains of influenza virus like H1N1, H3N2, H1N9, H7N9, etc. in every season of flu is mainly due to frequent mutation in eight genes of flu virus. This cause influenza virus spreads worldwide and become pandemic in 2009. Every year 36000 peoples are infected from flu. Around 123397 people have been tested itself in India in 2010. Drug for influenza treatment now has been resistance due to mutation in receptor of neuraminidase. Mutation is the major problem for designing inhibitor against influenza virus. Number of strains produced due genetic reassortment and mutant property of virus. This makes the different strains of hemagglutinin (H) and neuraminidase (N). Total eight gene of influenza virus, out of these only few gene involve for mutation continuously in which may be some beneficial or may some insensitive to flu. Gene mutation causes specific changes in sequence of the amino acids, and changes the conformation of other concerned residues which causing the unfitting binding site for influenza inhibitor. Number of other mutation associates with specific mutation like H274Y, N294S, I223R, E119V, Q136K and S31N etc. are responsible for changing conformation of binding site. Some mutation of surface protein of virus may cause negative or positive effect on binding site. Some induced mutation also helps in antiviral activity. This review highlights the mutation which causes resistance and changing residues in the binding site of in neuraminidase, hemagglutinin, and M2channel protein which would give the pathway for designing rational drug. Fig.2” Mechanism of drug-resistance and mutation in the neuraminidase amino acid (H274Y, R292K, N294S, or E119V. A shows the interaction of oseltamivir with wild type neraminidase receptor. B showing the interaction of oseltamivir with mutant type (274Y), and C showing the mechanism of mutation, how E276 rotate and make pocket for OST, and binds to R224. Histidine replaced by Tyrosine (bulkier residue) which changes the other residues conformation like E276, R292 so that E276 not rotate and oseltamivir not properly bind.