discovery of host-targeted covalent inhibitors of dengue virus：（登革热病毒的发现host-targeted共价抑制剂）.pdfVIP

Antiviral Research 139 (2017) 171e179 Contents lists available at ScienceDirect Antiviral Research journal homepage: /l ocate/antiviral Discovery of host-targeted covalent inhibitors of dengue virus a a b, c b, c Melissanne de Wispelaere , Margot Carocci , Yanke Liang , Qingsong Liu , Eileen Sun d, Michael L. Vetter a, Jinhua Wang b, c, Nathanael S. Gray b, c, Priscilla L. Yang a, * a Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA b Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA c Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA d Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA a r t i c l e i n f o a b s t r a c t Article history: We report here on an approach targeting the host reactive cysteinome to identify inhibitors of host Received 30 October 2016 factors required for the infectious cycle of Flaviviruses and other viruses. We used two parallel cellular Received in revised form phenotypic screens to identify a series of covalent inhibitors, exemplified by QL-XII-47, that are active 14 December 2016 against dengue virus. We show that the compounds effectively block viral protein expression and that Accepted 21 De