Fig. 4: Pharmacological inhibition of cGAS-STING limits SARS-CoV-2 mediated inflammatory pathway activation.

Cells were infected with SARS-CoV-2. One hour after infection cells were treated with the indicated drugs at the given concentrations. a–d Total RNA was isolated, and the indicated mRNA transcript levels were determined by RT-qPCR. Graphs show the average percent change and SEM for transcript levels compared to DMSO-treated cells for ≥3 independent experiments. e Protein levels from cell lysates were determined by western blotting. The graph shows the average percent change in protein levels in SARS-CoV-2 infected cells compared to mock. f–h A549-ACE2 cells were infected with SARS-CoV-2 for 1 h followed by treatment with the indicated drugs. 16 h after infection, cells were fixed and stained with antibodies directed against p65/RELA and IRF3. f Cells were imaged by confocal microscopy. White and yellow arrows indicate cells with positive or negative nuclear p65/RELA signals, respectively. Scale bars, 20 μm. g, h Graphs show the enrichment score for p65/RELA (g) or IRF3 (h) nuclear accumulation in cells treated with the indicated drugs. Graphs show the distribution of nuclear positive cells over three independent biological replicates. N > 4000 cells per condition. Box plots, box shows 25th–75th percentile; whiskers show min to max; line shows the mean value. Statistical significance was determined using one-way ANOVA with a Dunnett’s multiple comparison analysis. *represents statistical significance and exact p values are provided. For all panels, n ≥ 3 biological replicates.