title: High-throughput docking for the identification of new influenza A virus polymerase inhibitors targeting the PA-PB1 protein-protein interaction.
abstract: A high-throughput molecular docking approach was successfully applied for the selection of potential inhibitors of the Influenza RNA-polymerase which act by targeting the PA-PB1 protein-protein interaction. Commercially available compounds were purchased and biologically evaluated in vitro using an ELISA-based assay. As a result, some compounds possessing a 3-cyano-4,6-diphenyl-pyridine nucleus emerged as effective inhibitors with the best ones showing IC50 values in the micromolar range.
authors: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro, 53100 Siena, Italy.
authors: Cristina
authors: C
authors: Tintori
authors: IRCCS-Centro di Riferimento Oncologico Basilicata (CROB), Laboratory of Preclinical and Translational Research, Via Padre Pio 1, Rionero in Vulture, 85028 Potenza, Italy.
authors: Ilaria
authors: I
authors: Laurenzana
authors: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro, 53100 Siena, Italy; Dipartimento di Chimica e Tecnologie del Farmaco, Università La Sapienza, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
authors: Anna Lucia
authors: AL
authors: Fallacara
authors: PiKe Pharma GmbH, Institute of Pharmaceutical Sciences, Swiss Federal Institute for Technology, CH-8093 Zürich, Switzerland.
authors: Ulrich
authors: U
authors: Kessler
authors: PiKe Pharma GmbH, Institute of Pharmaceutical Sciences, Swiss Federal Institute for Technology, CH-8093 Zürich, Switzerland.
authors: Beatrice
authors: B
authors: Pilger
authors: PiKe Pharma GmbH, Institute of Pharmaceutical Sciences, Swiss Federal Institute for Technology, CH-8093 Zürich, Switzerland.
authors: Lilli
authors: L
authors: Stergiou
authors: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro, 53100 Siena, Italy; Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, BioLife Science Bldg., Suite 333, 1900 N 12th Street, Philadelphia, PA 19122, USA. Electronic address: botta.maurizio@gmail.com.
authors: Maurizio
authors: M
authors: Botta
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D009980:Influenza A virus / Q000201:enzymology*; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; C061290:PA protein, influenza viruses; C502893:PB2 protein, influenza virus; D011725:Pyridines; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Antiviral agents; High-throughput docking; Influenza virus; PA–PB1 interaction; Viral RNA polymerase; Virtual screening