Figure 7.
MTDB-imi6 inhibits SARS-CoV-2 replication in cells. (a, b) The percentage inhibition of viral replication normalized to vehicle treated cells (dashed line) after incubation with increasing concentrations of the pseudoknot degrader (MTDB-imi6) and control molecules (MTDB and TDB-imi6). Viral replication was assessed 24 h after infection [multiplicity of infection (MOI) of 0.05] based on the E gene and pseudoknot region RNA levels (n = 3). Antiviral activity of the MTDB-imi6 was observed when VERO-CCL-81 cells were treated before (a), or after infection (b), with SARS-CoV-2 at a 0.05 MOI. Mean ± SD of triplicates is shown, and differences between means with p < 0.01 are indicated. *p < 0.05; **p < 0.01; two-tailed paired t tests. (c) Calculated IC50 values of MTDB-imi6 when determined by quantifying E gene or the pseudoknot locus. (d) 24-h treatment with MTDB-imi6 at 6 μM showed a decreased number of viral plaques in comparison to vehicle treatment, both when added before or after infection. Control molecule MTDB showed only a decreased number of viral plaques when added before infection, and TDB-imi6 treatment showed no decrease in plaque formation. (e) None of the compounds showed cytotoxicity in VERO-CCL-81 cells (n = 3). Mean ± SD of triplicates is shown.