IN SILICO ANALYSIS OF HEMAGGLUTININ, NEURAMINIDASE, AND MATRIX2 OF H5N1 VIRUS INDONESIAN STRAIN RELATED TO ITS HIGH PATHOGENICITY

In the year of 2007, avian influenza outbreak which occurred in Indonesia caused mortality of almost 85% from detected avian influenza cases. Comparing the mortality rate in Indonesia to other countries with avian influenza outbreak, WHO announced that HPAI H5N1 Indonesia has the highest pathogenicity. Mutations with either antigenic shift or antigenic drift can influence the pathogenicity of influenza virus. Studies on hemagglutinin (HA), neuraminidase (NA), and matrix2 (M2) have been carried out because these three proteins have important roles in the infection process of avian influenza virus. In silico analysis was done by multiple alignment and phylogenetic tree construction. Hemagglutinin mutation was observed at the cleavage site and at the active site, while neuraminidase mutation and matrix2 mutation was observed at the active site. The amino acid character shift from hydrophilic to hydrophobic influenced the virus pathogenicity. The mutation analysis result was utilized for hemagglutinin cleavage by pro-P prediction, 3-D structure prediction, molecular docking simulation, and molecular dynamics simulation. Based on mutation analysis on hemagglutinin cleavage site, a R-X-K/R-R pattern was obtained for H5N1 Indonesia and H5N1 HongKong. Pro-P prediction results showed that the pattern which causes hemagglutinin HPAI H5N1 could be easily cut by Furin. 3-D structure analysis using molecular docking and molecular dynamics also showed that hemagglutinin and neuraminidase H5N1 Indonesia bind better with human sialic acid receptor. Meanwhile H5N1 virus's matrix2 protein gave resistance to amantadine and rimantadine. Results from the analysis revealed a relation between hemagglutinin, neuraminidase, and matrix2 mutation with the pathogenicity of H5N1 in Indonesia.