title: Peptide-mediated interference with influenza A virus polymerase.
abstract: The assembly of the polymerase complex of influenza A virus from the three viral polymerase subunits PB1, PB2, and PA is required for viral RNA synthesis. We show that peptides which specifically bind to the protein-protein interaction domains in the subunits responsible for complex formation interfere with polymerase complex assembly and inhibit viral replication. Specifically, we provide evidence that a 25-amino-acid peptide corresponding to the PA-binding domain of PB1 blocks the polymerase activity of influenza A virus and inhibits viral spread. Targeting polymerase subunit interactions therefore provides a novel strategy to develop antiviral compounds against influenza A virus or other viruses.
authors.affiliation: Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ghanem
authors.forename: Daniel
authors.initials: D
authors.lastname: Mayer
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Chase
authors.forename: Werner
authors.initials: W
authors.lastname: Tegge
authors.forename: Ronald
authors.initials: R
authors.lastname: Frank
authors.forename: Georg
authors.initials: G
authors.lastname: Kochs
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Martin
authors.initials: M
authors.lastname: Schwemmle
mesh_terms: D000595:Amino Acid Sequence; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000378:metabolism*; D009980:Influenza A virus / Q000201:enzymology* / Q000502:physiology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D010455:Peptides; D012321:DNA-Directed RNA Polymerases