title: Sialic acid-mimic peptides as hemagglutinin inhibitors for anti-influenza therapy.
abstract: Influenza is an infectious disease caused by the influenza virus, and each year many people suffer from this disease. Hemagglutinin (HA) in the membrane of type A influenza viruses recognizes sialylglycoconjugate receptors on the host cell surface at an initial step in the infection process; consequently, HA inhibitors are considered potential candidates for antiviral drugs. We identified peptides that bind to receptor-binding sites through a multiple serial selection from phage-displayed random peptide libraries. Using the HA of the H1 and H3 strains as target proteins, we obtained peptides that bind to both HAs. The binding affinities of peptides for these HAs were improved by secondary and tertiary selections from the corresponding sublibraries. A docking simulation suggested that, similar to sialic acid, the peptides are recognized by the receptor-binding site in HA, which indicates that these peptides mimic the sialic acid structure. N-stearoyl peptides inhibited infections by the A/Puerto Rico/8/34 (H1N1) and A/Aichi/2/68 (H3N2) strains of influenza virus. Such HA-inhibitors are promising candidates for novel antiviral drugs.
authors.affiliation: Department of Biosciences and Informatics, Keio University, Yokohama 223-8522, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Matsubara
authors.forename: Ai
authors.initials: A
authors.lastname: Onishi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Saito
authors.forename: Aki
authors.initials: A
authors.lastname: Shimada
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inoue
authors.forename: Takao
authors.initials: T
authors.lastname: Taki
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okahata
authors.forename: Toshinori
authors.initials: T
authors.lastname: Sato
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D017124:Conserved Sequence; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010455:Peptides; D054852:Small Molecule Libraries; C483468:hemagglutinin, human influenza A virus; D019158:N-Acetylneuraminic Acid