Anno2014
AutoriCroci, Romina; Tarantino, Delia; Milani, Mario; Pezzullo, Margherita; Rohayem, Jacques; Bolognesi, Martino; Mastrangelo, Eloise
AbstractNorovirus (NV) is a major cause of gastroenteritis worldwide. Antivirals against such important pathogens are on demand. Among the viral proteins that orchestrate viral replication, RNA-dependent-RNA-polymerase (RdRp) is a promising drug development target. From an in silico-docking search focused on the RdRp active site, we selected the compound PPNDS, which showed low micromolar IC50 vs. murine NV-RdRp in vitro. We report the crystal structure of the murine NV-RdRp/PPNDS complex showing that two molecules of the inhibitor bind in antiparallel stacking interaction, properly oriented to block exit of the newly synthesized RNA. Such inhibitor-binding mode mimics two stacked nucleotide-bases of the RdRp/ssRNA complex. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
RivistaFebs Letters (print)
ISSN0014-5793
Impact factor0
Volume588
Pagina inizio1720
Pagina fine1725
Autori IBFEloise MASTRANGELO, Mario MILANI, Delia TARANTINO
Linee di Ricerca IBFMD.P01.005.001
Sedi IBFIBF.MI