title: Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus.
abstract: Bovine lactoferrin (bLf) is a multifunctional glycoprotein that plays an important role in innate immunity against infections, including influenza. Here we have dissected bLf into its C- and N-lobes and show that inhibition of influenza virus hemagglutination and  cell infection is entirely attributable to the C-lobe and that all major virus subtypes, including H1N1 and H3N2, are inhibited. By far-western blotting and sequencing studies, we demonstrate that bLf C-lobe strongly binds to the HA(2) region of viral hemagglutinin, precisely the  highly conserved region containing the fusion peptide. By molecular docking studies, three C-lobe fragments were identified which inhibited virus hemagglutination and infection at fentomolar concentration range. Besides contributing to explain the broad anti-influenza activity of bLf, our  findings lay the foundations for exploiting bLf fragments as source of potential anti-influenza therapeutics.
authors.affiliation: Department of Technology and Health, National Institute of Health, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ammendolia
authors.forename: Mariangela
authors.initials: M
authors.lastname: Agamennone
authors.forename: Agostina
authors.initials: A
authors.lastname: Pietrantoni
authors.forename: Fabio
authors.initials: F
authors.lastname: Lannutti
authors.forename: Rosa Anna
authors.initials: RA
authors.lastname: Siciliano
authors.forename: Beatrice
authors.initials: B
authors.lastname: De Giulio
authors.forename: Carla
authors.initials: C
authors.lastname: Amici
authors.forename: Fabiana
authors.initials: F
authors.lastname: Superti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006388:Hemagglutinins / Q000378:metabolism; D007781:Lactoferrin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D016415:Sequence Alignment
chemical_list: D000998:Antiviral Agents; D006388:Hemagglutinins; D010446:Peptide Fragments; D007781:Lactoferrin