id author title date pages extension mime words sentences flesch summary cache txt cord-257511-4ftedh1a Gunaratne, Gihan S. NAADP-dependent Ca2+ signaling regulates Middle East respiratory syndrome-coronavirus pseudovirus translocation through the endolysosomal system 2018-11-30 .txt text/plain 7982 462 44 Knockdown of endogenous two-pore channels (TPCs), targets for the Ca2+ mobilizing second messenger NAADP, impaired infectivity in a MERS-CoV spike pseudovirus particle translocation assay. This inhibitory effect was dependent on appropriate subcellular targeting of the active channel as overexpression of a functional TPC2 channel rerouted from acidic Ca 2+ stores to the cell surface (TPC2pm, [25] ) by deletion of the NH 2 -terminal lysosomal targeting motif did not inhibit MERS-CoV pseudovirus infectivity (Fig. 2A) . To examine the effects of TPC regulators on MERS-CoV pseudovirus translocation, a fixed concentration (10μM) primary drug screen was performed in Huh7 cells, with the goal of identifying plasma membrane-permeable compounds with inhibitory activity on MERS-CoV pseudovirus translocation. Addition of the PIKfyve inhibitor YM201636 to reduce PI(3,5)P 2 levels, a phosphoinositide which activates TPC channels, decreased MERS-CoV pseudovirus translocation ( Supplementary Fig. 6 A&B) . ./cache/cord-257511-4ftedh1a.txt ./txt/cord-257511-4ftedh1a.txt