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

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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.

The studied mutations of neuraminidase and their influence to zanamivir binding

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No: 20905033) and the Fundamental Research Funds for the Central Universities (Grant No: lzujbky-2009-97). The authors also would like to thank the Gansu Computing Center for providing the computing resources.

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Authors and Affiliations

  1. School of Pharmacy, Lanzhou University, Lanzhou, 730000, China

    Dabo Pan, Chongliang Bai & Huanxiang Liu

  2. State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou, 730000, China

    Huijun Sun, Huanxiang Liu & Xiaojun Yao

  3. Gansu Computing Center, Lanzhou, 730030, China

    Yulin Shen & Nengzhi Jin

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  1. Dabo Pan
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  2. Huijun Sun
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  3. Chongliang Bai
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  4. Yulin Shen
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  6. Huanxiang Liu
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Correspondence to Huanxiang Liu.

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Pan, D., Sun, H., Bai, C. et al. Prediction of zanamivir efficiency over the possible 2009 Influenza A (H1N1) mutants by multiple molecular dynamics simulations and free energy calculations. J Mol Model 17, 2465–2473 (2011). https://doi.org/10.1007/s00894-010-0929-8

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  • DOI: https://doi.org/10.1007/s00894-010-0929-8

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