Fig. 5: CAV-F6 R54S mutation reduces binding affinity and consequentially diminishes inhibition potency.
From: Broad neuraminidase antibodies confer protection against seasonal and avian influenza viruses
A, B Two-dimensional classification and three-dimensional models of the A/Switzerland/9715293/2013 (H3N2) in complex with CAV-F6 (A) and CAV-F34 (B). C Comparison of key amino acid sites between CAV-F34 and CAV-F6 binding to the A/Switzerland/9715293/2013 (H3N2) NA tetramer. Hydrogen bonds and salt bridge interactions formed between NA and CAV-F6 are marked with blue triangles, while those with CAV-F34 are marked with orange inverted triangles. Amino acid residues that form plenty of contacts with NA are marked with black circles. D The IC50 value of enzyme inhibitory ability of CAV-F6 and its single point mutant including R54S, D102N and W105L against A/Switzerland/9715293/2013 (H3N2) NA protein via ELLA and MUNANA assay. E–G Binding affinity of CAV-F34, CAV-F6 and CAV-F6 R54S with A/Switzerland/9715293/2013 (H3N2) NA via BLI assay. H, I Detailed interactions between the wild-type CAV-F6-R54 residue (H) and mutated CAV-F6-R54S residue (I) with the A/Switzerland/9715293/2013 (H3N2) NA protomer. Salt bridges and hydrogen bonds are depicted by solid lines. J Superimposition of the CAV-F6-R54S fab and the unbounded NA protomer of the A/Switzerland/9715293/2013 (H3N2) NA/CAV-F6-R54S complex displayed an obvious steric hindrance. K Superimposition of the CAV-F6-R54S fab of the A/Switzerland/9715293/2013 (H3N2) NA/CAV-F6-R54S complex and the protomer of apo A/Switzerland/9715293/2013 (H3N2) NA tetramer also displayed a similar steric hindrance. L Fold change in IC50 values for CAV-F6-R54S and CAV-F6 in NAI of A/Switzerland/9715293/2013 (H3N2) NA with different mutations. M–Q Inhibitory activity of CAV-F6-R54S and CAV-F6 against N2 NA carrying K199R, K199A, K199D, K199E mutations in MUNANA assay. Data represents one of three independent experiments, shown as mean ± SD of three technical replicates.
