Figure 10.

Compound 1111684 alters VEEV capsid distribution and inhibits viral replication. (A) Vero cells were treated with serial dilutions of 1111684 in the vehicle DMSO. Luminescence was measured using the Promega CellGlo Viability Assay (see Materials and Methods) at 24 h post-treatment. Data represent the mean ± SD (n = 4) luminescence as a percentage normalized to that of DMSO-treated cells. (B) Vero cells were pretreated with DMSO or increasing concentrations of 1111684 2 h prior to infection, and then infected with VEEV-TC83luc at a multiplicity of infection (MOI) of 1 in the continued presence of 1111684. The BrightGlo Luciferase Assay was performed at 16 h post-infection (p.i.). Data represent the mean ± SD (n = 4) luminescence as a percentage normalized to that of DMSO-treated cells. (C) Vero cells were pretreated with DMSO (0.1%) with or without Mifepristone or 1111684 (10 μM) for 2 h prior to infection with VEEV-TC83 at an MOI of 0.1 in the continued presence of the respective inhibitors. Mock-infected cells were untreated and uninfected. At 16 h p.i., cells were fixed and probed for C (red) and DAPI stained (blue). Nuclear to cytoplasmic fluorescence ratios (Fn/c) were determined as previously^18,20 (right). **p < 0.005; ***p < 0.0001.