Fig. 6.
Targeting cGAS-STING pathway as potential therapeutics against SARS-CoV-2. a Effect of cGAS expression on SARS-CoV-2 replication. Wildtype HeLa-ACE2 (WT), HeLa-cGASKO-ACE2, and HeLa-cGASRE-ACE2 cells were infected with SARS-CoV-2 at an MOI of 0.5. At indicated times, total RNA extracted from cells was evaluated by quantitative PCR. The data are expressed as fold changes of the RNA levels of the viral N gene relative to the GAPDH control. Mean ± s.d., n = 3. *P < 0.05, **P < 0.01, ****P < 0.0001, n.s. not significant. Two-tailed Student’s t-test. b The chemical structure of diABZI. c, d Antiviral effect of diABZI on SARS-CoV-2. Calu-3 (c) or HeLa-ACE2 (d) cells were treated with serially diluted diABZI for 24 h (Calu-3) or 1 h (HeLa-ACE2). Cells were then subjected to viability assay or infected with SARS-CoV-2 at an MOI of 0.2. After 24 h (Calu-3) or 48 h (HeLa-ACE2), supernatants were harvested for RNA extraction, followed by absolute quantification of viral N mRNA by PCR. Mean ± s.d., n = 4. The IC50 (the half-maximal inhibitory concentration) and CC50 (the half-maximal cytotoxic concentration) values were calculated using Prism software. Lower panels showed diABZI-induced STING and IRF3 activation. Calu-3 (c) or HeLa-ACE2 (d) cells were treated with serially diluted diABZI for 24 h and 6 h, respectively, followed by Western blot analysis using indicated antibodies