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

Nature. 2006 Sep 7;443(7107):45-9. doi: 10.1038/nature05114. Epub 2006 Aug 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / metabolism
  • Acetamides / pharmacology
  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology
  • Binding Sites
  • Birds / virology
  • Drug Design*
  • Drug Resistance, Viral / genetics
  • Humans
  • Influenza A Virus, H5N1 Subtype / classification
  • Influenza A Virus, H5N1 Subtype / drug effects
  • Influenza A Virus, H5N1 Subtype / enzymology*
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza in Birds / drug therapy*
  • Influenza in Birds / virology
  • Models, Molecular
  • Mutation / genetics
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / chemistry*
  • Neuraminidase / classification
  • Neuraminidase / genetics
  • Oseltamivir
  • Protein Conformation


  • Acetamides
  • Antiviral Agents
  • Oseltamivir
  • Neuraminidase

Associated data

  • PDB/2HT5
  • PDB/2HT7
  • PDB/2HT8
  • PDB/2HTQ
  • PDB/2HTR
  • PDB/2HTU
  • PDB/2HTV
  • PDB/2HTW
  • PDB/2HTY
  • PDB/2HU0
  • PDB/2HU4