کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2823128 | 1161371 | 2011 | 11 صفحه PDF | دانلود رایگان |
Antigenic drift causes number of mutations in neuraminidase protein of H1N1 swine influenza virus. We analyzed neuraminidase mutations in H1N1 strains distributed over six continents, at both the sequence and structural level. Mutations in the nearby residues of the drug binding site play crucial role in the binding affinity of the drug with the protein. For this purpose, mutant models were generated for the neuraminidase protein from 34 pandemic H1N1 isolates and docking were performed with zanamivir drug. Multiple sequence alignment (MSA) and variations in docking score suggest that there are considerable changes in the binding affinity of neuraminidase with zanamivir, which leads to probable ineffectiveness of zanamivir in the isolated samples of pandemic H1N1 collected from quite a few countries. To further evaluate the effectiveness of the antiviral drugs, we derived, calibrated and analyzed an ordinary differential equations based mathematical model for H1N1 infection dynamics and drug mediated virus deactivation.
► All the circulating mutations in neuraminidase protein of H1N1 were analyzed for their impact on drug binding affinity.
► Detail structural variations were investigated due to circulating mutations.
► Docking studies were integrated with mathematical models to identify effectiveness of zanamivir targeting NA protein.
► Viral population dynamics were analyzed in zanamivir resistant/ susceptible strains using simulation studies.
Journal: Infection, Genetics and Evolution - Volume 11, Issue 5, July 2011, Pages 1072–1082