| Abstract: | The pandemic influenza AH1N1 (2009) caused an outbreak of human infection that spread to the world. Neuraminidase (NA) is anantigenic surface glycoprotein, which is essential to the influenza infection process, and is the target of anti-flu drugs oseltamivirand zanamivir. Currently, NA inhibitors are the pillar pharmacological strategy against seasonal and global influenza. Althoughmutations observed after NA-inhibitor treatment are characterized by changes in conserved amino acids of the enzyme catalyticsite, it is possible that specific amino acid substitutions (AASs) distant from the active site such as H274Y, could confer oseltamiviror zanamivir resistance. To better understand the molecular distribution pattern of NA AASs, we analyzed NA AASs from allavailable reported pandemic AH1N1 NA sequences, including those reported from America, Africa, Asia, Europe, Oceania, andspecifically from Mexico. The molecular distributions of the AASs were obtained at the secondary structure domain level for boththe active and catalytic sites, and compared between geographic regions. Our results showed that NA AASs from America, Asia,Europe, Oceania and Mexico followed similar molecular distribution patterns. The compiled data of this study showed that highlyconserved amino acids from the NA active site and catalytic site are indeed being affected by mutations. The reported NA AASsfollow a similar molecular distribution pattern worldwide. Although most AASs are distributed distantly from the active site, thisstudy shows the emergence of mutations affecting the previously conserved active and catalytic site. A significant number ofunique AASs were reported simultaneously on different continents. |
