(A to D) Vero-E6 cells were pretreated with the indicated concentration of Cathepsin L inhibitor Calpain Inhibitor III (A), PIKfyve inhibitor APY0201 (B) SMARCA4 inhibitor PFI-3 (C), SMAD3 inhibitor SIS3 (D) for 48 hours and then infected with SARS-CoV-2 at a MOI of 0.2. Cell viability was measured at 3dpi and compared to mock infected controls. Red, infected; blue, mock (E to F) Vero-E6 cells were pretreated with 10 μM Calpain inhibitor III, PFI-3 or SIS3 for 48 hours and then infected with icSARS-CoV-2 mNG at a MOI of 1. Infected cell frequencies were measured by mNeonGreen expression at 2 dpi. Data were analyzed by one-way ANOVA with Tukey’s multiple comparison test.. Shown are means ± SEM. ns, not statistically significant; *P < 0.05; **P < 0.01; ***P < 0.001. Data are pooled from two independent experiments each in duplicate except in (E), where results are shown from one representative experiment.