Grafting Methionine on 1F1 Ab Increases the Broad-Activity on HAStructural-Conserved Residues of H1 H2 and H3 Influenza aViruses

摘要

A high level of mutation enables the influenza A virus to resist antibioticspreviously effective against the influenza A virus. A portion of the structureof hemagglutinin HA is assumed to be well-conserved to maintain its role incellular fusion, and the structure tends to be more conserved than sequence. Wedesigned peptide inhibitors to target the conserved residues on the HA surface,which were identified based on structural alignment. Most of the conserved andstrongly similar residues are located in the receptor-binding and esteraseregions on the HA1 domain In a later step, fragments of anti-HA antibodies weregathered and screened for the binding ability to the found conserved residues.As a result, Methionine amino acid got the best docking score within the −2.8 Åradius of Van der Waals when it is interacting with Tyrosine, Arginine, andGlutamic acid. Then, the binding affinity and spectrum of the fragments wereenhanced by grafting hotspot amino acid into the fragments to form peptideinhibitors. Our peptide inhibitor was able to form in silico contact with astructurally conserved region across H1, H2, and H3 HA, with the binding site atthe boundary between HA1 and HA2 domains, spreading across different monomers,suggesting a new target for designing broad-spectrum antibody and vaccine. Thisresearch presents an affordable method to design broad-spectrum peptideinhibitors using fragments of an antibody as a scaffold.