Influenza Viral Hemagglutinin Peptide Inhibits Influenza Viral Entry by Shielding the Host Receptor

Influenza viral infection of the host begins by the attachment of viral hemagglutinin to a cell surface receptor. In the current study, a hemagglutinin fragment peptide library was screened using an H5N1 recombinant pseudotyped viral system. One peptide, designated HA-pep25, showed effective antiviral activity against both human and avian influenza viral strains (IC50 = 12.0–51.0 μM). A mechanistic study demonstrated direct binding between HA-pep25 and sialyllactose, which mimics the host receptor for the influenza virus. This binding was independent of the presence of sialic acid on the cell membrane. By generating alanine substitutions in HA-pep25, eight residues were identified as essential for the peptide's anti-influenza activity. HA-pep25 derived from hemagglutinin blocked influenza viral entry by shielding the host receptor on the cell membrane. This peptide might be a candidate drug for influenza virus entry inhibition and may be combined with other antivirals targeting different steps of the influenza viral life cycle.