Fig. 6: UNI418 inhibits ACE2 receptor-mediated viral entry.
From: A dual inhibitor of PIP5K1C and PIKfyve prevents SARS-CoV-2 entry into cells
a SARS-CoV-2 infection-induced ACE2 downregulation was assessed in Vero cells. The cells were infected with SARS-CoV-2 at the indicated concentrations of UNI418 and subjected to Western blot analysis of ACE2, its cleaved ectodomain (ACE2ecto) and GAPDH at 1 and 3 h postinfection. b Endocytosis of ACE2 triggered by the interaction of ACE2 with the spike RBD protein (spike-RBD) was examined using 0.1 mM dynasore and 0.5 μM UNC3230, apilimod and UNI418. HEK293T cells were transfected with hACE2-GFP, treated with each compound and subjected to live cell imaging at the indicated times to visualize the hACE-GFP distribution. Membrane-bound ACE2 and internalized ACE2 are marked with yellow and white arrows, respectively. Scale bar, 10 µm. c The area ratio of internalized to membranous hACE2-GFP in individual cells was quantified and is presented as the mean ± SEM, n > = 20. Statistical significance was determined by one-way ANOVA; ***p < 0.001 and n.s., not significant.
