title: Towards strain-independent anti-influenza peptides: a SAXS- and modeling-based study.
abstract: Using small angle X-ray scattering (SAXS) data, we reconstructed the scattering shape of the Hemagglutinin (HA) trimer protein from five different influenza strains. Comparison with the known crystal structures-based information aided in identifying volumes pertaining to the glycosylation in the HA trimers. By merging sequence information on HA proteins from pathogenic strains of influenza, we identified a novel druggable pocket composed of residues which remained conserved during evolution, lack propensity to be glycosylated, and play important role in maintaining interchain contacts in the pH-sensitive head group. To test our hypothesis that molecules reactive to this site may retard pH-induced opening of HA trimer in strain-independent manner, we performed in vitro screening of peptides representing interacting epitopes for their ability to retard pH-induced opening of HA trimers. Results brought forth that some of the 20 peptides tested can retard low pH-induced opening/association of HA proteins across different subtypes, thus propagating notion that the drug site and peptides identified here may pave way towards strain-independent anti-influenza molecules.
authors.affiliation: a CSIR-Institute of Microbial Technology , Chandigarh , 160036 , India .
authors.forename: Kalpana
authors.initials: K
authors.lastname: Pandey
authors.forename: Yogendra S
authors.initials: YS
authors.lastname: Rathore
authors.forename: Samir K
authors.initials: SK
authors.lastname: Nath
authors.lastname: Ashish
mesh_terms: D000595:Amino Acid Sequence; D006031:Glycosylation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D055503:Protein Multimerization; D053838:Scattering, Small Angle; D013045:Species Specificity
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D019151:Peptide Library; D010455:Peptides
keywords: drug site; glycosylation; hemagglutinin trimer; influenza; normal mode analysis; peptide design; sequence alignment; small angle X-ray scattering