A new class of synthetic anti-lipopolysaccharide peptides inhibits influenza A virus replication by blocking cellular attachment.
Influenza A viruses are a continuous threat to human health as illustrated by the 2009 H1N1 pandemic. Since circulating influenza virus strains become increasingly resistant against currently available drugs, the development of novel antivirals is urgently needed. Here, we have evaluated a recently described new class of broad-spectrum antiviral peptides (synthetic anti-lipopolysaccharide peptides; SALPs) for their potential to inhibit influenza virus replication in vitro and in vivo. We found that particularly SALP PEP 19-2.5 shows high binding affinities for the influenza virus receptor molecule, N-Acetylneuraminic acid, leading to impaired viral attachment and cellular entry. As a result, replication of several influenza virus subtypes (H7N7, H3N2 and 2009 pandemic H1N1) was strongly reduced. Furthermore, mice co-treated with PEP 19-2.5 were protected against an otherwise 100% lethal H7N7 influenza virus infection. These findings show that SALPs exhibit antiviral activity against influenza viruses by blocking virus attachment and entry into host cells. Thus, SALPs present a new class of broad-spectrum antiviral peptides for further development for influenza virus therapy.
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistr. 52, 20251 Hamburg, Germany.
Julia
J
Hoffmann
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistr. 52, 20251 Hamburg, Germany.
Carola
C
Schneider
Leibniz-Center for Medicine and Biosciences, Research Center Borstel, Parkallee 35, 23845 Borstel, Germany.
Lena
L
Heinbockel
Leibniz-Center for Medicine and Biosciences, Research Center Borstel, Parkallee 35, 23845 Borstel, Germany.
Klaus
K
Brandenburg
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistr. 52, 20251 Hamburg, Germany.
Rudolph
R
Reimer
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistr. 52, 20251 Hamburg, Germany. Electronic address: guelsah.gabriel@hpi.uni-hamburg.de.
Gülsah
G
Gabriel
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D006384:Hemagglutination / Q000187:drug effects; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000821:virology; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D053585:Virus Attachment / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D008070:Lipopolysaccharides; D010455:Peptides; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid
Cellular attachment inhibitor; Influenza virus; Mouse model; Synthetic anti-lipopolysaccharide peptides (SALPs)