Blocking influenza hemagglutinin

The interaction between sialic acid receptors on host cell membranes and a specific viral protein can be targeted by natural antibodies to block influenza virus infections. The findings, published online this week in Nature Structural & Molecular Biology, hold potential for how therapeutic drugs can mimic the same interaction.

Ian Wilson, James Crowe and colleagues have obtained X-ray snapshots of three different neutralizing antibodies, each bound to the viral protein hemagglutinin (HA) from the strain H2N2. All three antibodies plug a cavity within the receptor binding site of HA, using the same mechanism and contacting a residue that is conserved across all influenza strains.

Sialic acid analogs have been investigated in the past as potential flu inhibitors, but with little success. Together with previous structures, the work here reveals a pocket for the development of new inhibitors, using either small proteins or small-molecule compounds.