Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion

Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17736-41. doi: 10.1073/pnas.0807142105. Epub 2008 Nov 12.


The influenza surface glycoprotein hemagglutinin (HA) is a potential target for antiviral drugs because of its key roles in the initial stages of infection: receptor binding and the fusion of virus and cell membranes. The structure of HA in complex with a known inhibitor of membrane fusion and virus infectivity, tert-butyl hydroquinone (TBHQ), shows that the inhibitor binds in a hydrophobic pocket formed at an interface between HA monomers. Occupation of this site by TBHQ stabilizes the neutral pH structure through intersubunit and intrasubunit interactions that presumably inhibit the conformational rearrangements required for membrane fusion. The nature of the binding site suggests routes for the chemical modification of TBHQ that could lead to the development of more potent inhibitors of membrane fusion and potential anti-influenza drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Fluorometry
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hydrogen-Ion Concentration / drug effects
  • Hydroquinones / chemistry*
  • Hydroquinones / pharmacology*
  • Membrane Fusion / drug effects*
  • Phylogeny
  • Protein Multimerization / drug effects
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Substrate Specificity / drug effects


  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hydroquinones
  • Protein Subunits
  • 2-tert-butylhydroquinone

Associated data

  • PDB/3EYJ
  • PDB/3EYK
  • PDB/3EYM