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The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design

Author

Listed:
  • Rupert J. Russell

    (MRC National Institute for Medical Research, The Ridgeway
    University of St Andrews)

  • Lesley F. Haire

    (MRC National Institute for Medical Research, The Ridgeway)

  • David J. Stevens

    (MRC National Institute for Medical Research, The Ridgeway)

  • Patrick J. Collins

    (MRC National Institute for Medical Research, The Ridgeway)

  • Yi Pu Lin

    (MRC National Institute for Medical Research, The Ridgeway)

  • G. Michael Blackburn

    (University of Sheffield)

  • Alan J. Hay

    (MRC National Institute for Medical Research, The Ridgeway)

  • Steven J. Gamblin

    (MRC National Institute for Medical Research, The Ridgeway)

  • John J. Skehel

    (MRC National Institute for Medical Research, The Ridgeway)

Abstract

The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs.

Suggested Citation

  • Rupert J. Russell & Lesley F. Haire & David J. Stevens & Patrick J. Collins & Yi Pu Lin & G. Michael Blackburn & Alan J. Hay & Steven J. Gamblin & John J. Skehel, 2006. "The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design," Nature, Nature, vol. 443(7107), pages 45-49, September.
    • Handle: RePEc:nat:nature:v:443:y:2006:i:7107:d:10.1038_nature05114
    DOI: 10.1038/nature05114
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    Cited by:

    1. Kyle T Greenway & Eric B LeGresley & B Mario Pinto, 2013. "The Influence of 150-Cavity Binders on the Dynamics of Influenza A Neuraminidases as Revealed by Molecular Dynamics Simulations and Combined Clustering," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-15, March.

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