Journal of Molecular Modeling

, Volume 17, Issue 3, pp 587–592 | Cite as

Molecular dynamics simulation of oseltamivir resistance in neuraminidase of avian influenza H5N1 virus

  • Mao Shu
  • Zhihua Lin
  • Yunru Zhang
  • Yuqian Wu
  • Hu Mei
  • Yongjun Jiang
Original Paper

Abstract

The outbreak of avian influenza virus H5N1 has raised a global concern because of its high virulence and mutation rate. Although two classes of antiviral drugs, M2 ion channel protein inhibitors and neuraminidase inhibitors, are expected to be important in controlling the early stages of a potential pandemic. Different strains of influenza viruses have differing degrees of resistance against the antivirals. In order to analyze the detailed information on the viral resistance, molecular dynamics simulations were carried out for the neuraminidase (NA) complex with oseltamivir. The carboxylate of Glu276 of H252Y NA faces toward the O-ethyl-propyl group of oesltamivir, Glu276 of wild-type NA adopts a conformation pointing away from the oesltamivir. τ2 and τ3 torsional angles fluctuation of the oesltamivir are relatively high for the H252Y mutant NA complex. In addition, there are fewer hydrogen bonds between the oesltamivir and H252Y mutation NA. The results show that H252Y mutation NA has high resistance against the drug.

Keywords

Influenza virus Molecular dynamics simulations Neuraminidase Oseltamivir 

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 60873103), and supported by the Key Project of Natural Science Foundation of China (No. 30830090), and supported by Program for New Century Excellent Talents in University (No.NCET-06-0780), and supported by Visitorg Scholar Foundation of Key Laboratory of Biorheological Science and Technology (No. 2009BST03).

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Mao Shu
    • 1
  • Zhihua Lin
    • 1
  • Yunru Zhang
    • 1
  • Yuqian Wu
    • 2
  • Hu Mei
    • 2
  • Yongjun Jiang
    • 3
  1. 1.College of Pharmacy and BioengineeringChongqing University of TechnologyChongqingPeople’s Republic of China
  2. 2.College of BioengineeringChongqing UniversityChongqingPeople’s Republic of China
  3. 3.Key Laboratory for Molecular Design and Nutrition Engineering of Ningbo City, Ningbo Institute of TechnologyZhejiang UniversityNingboPeople’s Republic of China

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