title: Identification of influenza virus inhibitors which disrupt of viral polymerase protein-protein interactions.
abstract: Due to their ability to rapidly mutate, influenza viruses quickly develop resistance against many antiviral substances, leading to an urgent need for new compounds. The trimeric viral polymerase complex, a major target for the development of new inhibitors, must be assembled from the PB1, PB2, and PA subunits for successful infection. Here, we describe ELISA-based assays which allow the identification of peptides which impair polymerase complex formation. Since the protein-protein interaction domains of the viral polymerase are highly conserved, these inhibitors are also predicted to be active against a broad range of influenza strains. Using this method, identification of small molecules and lead compounds against influenza A and B viruses should be feasible.
authors.affiliation: Department of Virology, Universitätsklinikum Freiburg, Germany.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Chase
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wunderlich
authors.forename: Peter
authors.initials: P
authors.lastname: Reuther
authors.forename: Martin
authors.initials: M
authors.lastname: Schwemmle
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001667:Binding, Competitive; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D009975:Orthomyxoviridae / Q000187:drug effects*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; C061290:PA protein, influenza viruses; C502893:PB2 protein, influenza virus; D010446:Peptide Fragments; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; D012324:RNA-Dependent RNA Polymerase