A nanomolar multivalent ligand as entry inhibitor of the hemagglutinin of avian influenza

J Am Chem Soc. 2014 Jan 15;136(2):783-8. doi: 10.1021/ja410918a. Epub 2014 Jan 7.


Influenza virus attaches itself to sialic acids on the surface of epithelial cells of the upper respiratory tract of the host using its own protein hemagglutinin. Species specificity of influenza virus is determined by the linkages of the sialic acids. Birds and humans have α2-3 and α2-6 linked sialic acids, respectively. Viral hemagglutinin is a homotrimeric receptor, and thus, tri- or oligovalent ligands should have a high binding affinity. We describe the in silico design, chemical synthesis and binding analysis of a trivalent glycopeptide mimetic. This compound binds to hemagglutinin H5 of avian influenza with a dissociation constant of K(D) = 446 nM and an inhibitory constant of K(I) = 15 μM. In silico modeling shows that the ligand should also bind to hemagglutinin H7 of the virus that causes the current influenza outbreak in China. The trivalent glycopeptide mimetic and analogues have the potential to block many different influenza viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • Glycopeptides / chemical synthesis
  • Glycopeptides / chemistry
  • Glycopeptides / metabolism*
  • Hemagglutinin Glycoproteins, Influenza Virus / drug effects*
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship


  • Glycopeptides
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Ligands