Potent sialic acid inhibitors that target influenza A virus hemagglutinin

Abstract Eradicating influenza A virus (IAV) is difficult, due to its genetic drift and reassortment ability. As the infectious cycle initiated by glycoprotein, hemagglutinin (HA), which mediates binding of virions terminal sialic acids moieties, HA a tempting target anti-influenza inhibitors. However, complexity structure has prevented delineation structural characterization protein–ligand complex. Our computational strategy efficiently analyzed > 200,000 records compounds held in United States National Cancer Institute (NCI) database identified potential inhibitors, modeling acid (SA) receptor site (RBS) for structure. revealed that compound NSC85561 showed significant antiviral activity against IAV H1N1 strain with EC 50 values ranging from 2.31 2.53 µM negligible cytotoxicity (CC 700 µM). Using as template generate 12 derivatives, robust bioassay results strongest efficacies NSC47715 NSC7223. Virtual screening clearly three SA inhibitors were successfully validated experimental data. Thus, our show IAV-associated activity.