title: A novel family of peptides with potent activity against influenza A viruses.
abstract: The emergence of drug-resistant strains of influenza virus has catalysed a search for new antiviral agents to supplement or replace existing drugs. Following the success of the human immunodeficiency virus entry blocker Enfuvirtide, there has been a resurgence of interest in peptide-based antivirals. In this paper, we report on the discovery of a novel family of peptides (FluPep, FP) that function as inhibitors of influenza A virus infection. The prototype peptide (FP1, also known as Tkip) interacts with haemagglutinin and inhibits the binding of the virus to cell membranes. Using a plaque-reduction assay, we have demonstrated that a variety of influenza A virus subtypes (including H1N1, H3N2 and H5N1) are inhibited by FluPep and its derivatives at nanomolar concentrations. By truncating FluPep we have identified a minimal sequence of 6 aa that binds to haemagglutinin and inhibits infection. Using a mouse model of intranasal influenza virus infection, we observed potent inhibition of virus infection when peptide is given at the time of virus administration. These data indicate that FluPep is a highly effective anti-influenza agent with the potential to translate to the clinic.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush EH25 9RG, UK.
authors.forename: Marlynne Q
authors.initials: MQ
authors.lastname: Nicol
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush EH25 9RG, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Ligertwood
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush EH25 9RG, UK.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Bacon
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush EH25 9RG, UK.
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Dutia
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush EH25 9RG, UK.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Nash
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects*; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000821:virology; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D010948:Viral Plaque Assay; D053585:Virus Attachment / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010455:Peptides