Inhibition of influenza virus infections by sialylgalactose-binding peptides selected from a phage library.

Abstract

Influenza virus hemagglutinin recognizes sialyloligosaccharides of glycoproteins and glycolipids as cell surface receptors in the initial stage of the infection process. We demonstrate that pentadecapeptides that bind to a sialylgalactose structure (Neu5Ac-Gal) inhibited the infection of cells by influenza virus. The pentadecapeptides were identified through affinity selection from a phage-displayed random peptide library using a monolayer of the ganglioside Neu5Acalpha2-3Galbeta1-4Glcbeta1-1'Cer (GM3). The peptides were found to have affinity for GM3, and alanine scanning showed seven amino acid residues that contribute to carbohydrate recognition. The binding of peptides to the cell surface was significantly inhibited in the presence of sialic acid or by the digestion of cell surface sialyl residues by neuraminidase. Plaque assays indicated that a molecular assembly of alkylated peptides inhibited the infection of Madin-Darby canine kidney cells by influenza virus. Carbohydrate-binding peptides that inhibit carbohydrate-virus interaction showed inhibitory activity. These results may lead to a new approach to the design of antiviral drugs.

• Authors: Teruhiko Matsubara, Machiko Sumi, Hiroyuki Kubota, Takao Taki, Yoshio Okahata, Toshinori Sato
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 52 Issue 14 Pg. 4247-56 (Jul 23 2009) ISSN: 1520-4804 [Electronic] United States
• PMID: 19558186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Gangliosides
• Peptide Library
• Peptides
• Sialoglycoproteins

Topics

• Alkylation
• Amino Acid Sequence
• Animals
• Antiviral Agents (chemistry, metabolism, pharmacology)
• Bacteriophages (metabolism)
• Carbohydrate Sequence
• Cell Line
• Dogs
• Drug Evaluation, Preclinical
• Enzyme-Linked Immunosorbent Assay
• Gangliosides (chemistry)
• Humans
• Influenza A virus (drug effects, physiology)
• Mice
• Molecular Sequence Data
• Mutagenesis
• Orthomyxoviridae Infections (drug therapy)
• Peptide Library
• Peptides (chemistry, genetics, metabolism, pharmacology)
• Sialoglycoproteins (chemistry, metabolism)
• Virus Attachment (drug effects)