☆ 4.4 Article

Prediction of zanamivir efficiency over the possible 2009 Influenza A (H1N1) mutants by multiple molecular dynamics simulations and free energy calculations

JOURNAL OF MOLECULAR MODELING (2011)

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期刊

JOURNAL OF MOLECULAR MODELING
卷 17, 期 10, 页码 2465-2473

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SPRINGER
DOI: 10.1007/s00894-010-0929-8

关键词

Drug resistance; 2009 H1N1 Influenza A virus; Molecular dynamics simulation; Molecular mechanics generalized Born surface area (MM-GBSA); Zanamivir

类别

Biochemistry & Molecular Biology Biophysics Chemistry, Multidisciplinary Computer Science, Interdisciplinary Applications

资金

  1. National Natural Science Foundation of China [20905033]
  2. Fundamental Research Funds for the Central Universities [Izujbky-2009-97]

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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.

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