Anno2016
AutoriTarantino D, Cannalire R, Mastrangelo E, Croci R, Querat G, Barreca ML, Bolognesi M, Manfroni G, Cecchetti V, Milani M
AbstractRNA dependent RNA polymerases (RdRp) are essential enzymes for flavivirus replication. Starting from an in silico docking analysis we identified a pyridobenzothiazole compound, HeE1-2Tyr, able to inhibit West Nile and Dengue RdRps activity in vitro, which proved effective against different flaviviruses in cell culture. Crystallographic data show that HeE1-2Tyr binds between the fingers domain and the priming loop of Dengue virus RdRp (Site 1). Conversely, enzyme kinetics, binding studies and mutational analyses suggest that, during the catalytic cycle and assembly of the RdRp-RNA complex, HeE1-2Tyr might be hosted in a distinct binding site (Site 2). RdRp mutational studies, driven by in silico docking analysis, allowed us to locate the inhibition Site 2 in the thumb domain. Taken together, our results provide innovative concepts for optimization of a new class of anti-flavivirus compounds.
RivistaAntiviral Research (print)
ISSN0166-3542
Impact factor
Volume134
Pagina inizio226
Pagina fine235
Autori IBFEloise MASTRANGELO, Martino BOLOGNESI, Delia TARANTINO
Linee di Ricerca IBFMD.P01.005.001
Sedi IBFIBF.MI