title: Prediction of zanamivir efficiency over the possible 2009 influenza A (H1N1) mutants by multiple molecular dynamics simulations and free energy calculations.
abstract: As one of the most important antiviral drugs against 2009 influenza A (H1N1), will zanamivir be effective for the possible drug resistant mutants? To answer this question, we combined multiple molecular dynamics simulations and molecular mechanics generalized Born surface area (MM-GBSA) calculations to study the efficiency of zanamivir over the most frequent drug-resistant strains of neuraminidase including R293K, R152K, E119A/D and H275Y mutants. The calculated results indicate that the modeled mutants of the 2009-H1N1 strains except H275Y will be significantly resistant to zanamivir. The resistance to zanamivir is mainly caused by the loss of polar interactions. The identified potential resistance sites in this study will be useful for the development of new effective anti-influenza drugs and to avoid the occurrence of the state without effective drugs to new mutant influenza strains.
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Dabo
authors.initials: D
authors.lastname: Pan
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.forename: Chongliang
authors.initials: C
authors.lastname: Bai
authors.forename: Yulin
authors.initials: Y
authors.lastname: Shen
authors.forename: Nengzhi
authors.initials: N
authors.lastname: Jin
authors.forename: Huanxiang
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yao
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics; D006801:Humans; D006860:Hydrogen Bonding; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000235:genetics*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D053243:Zanamivir / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D009439:Neuraminidase; D053243:Zanamivir