Fig. 7: Agents that reduce TMPRSS2 expression markedly inhibit SARS-CoV-2 pseudoviral infection. | Nature Communications

Fig. 7: Agents that reduce TMPRSS2 expression markedly inhibit SARS-CoV-2 pseudoviral infection.

From: A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry

Fig. 7

A Schematic of pseudoviral construction and assay. The S protein of SARS-CoV-2 was C-terminally tagged with HiBiT. B Level of viral transduction in various cell lines plotted on a logarithmic scale. Calu-3 and Caco-2 cells had the highest observed rates of infection. Data are mean ± SEM (n = 4–6 biologically independent samples). C Effects of HHT or HFG on pseudoviral-mediated GFP expression, determined by immunostaining, scale bar = 500 µm. D, E Effects of increasing concentrations of homoharringtonine (HHT) (D) or halofuginone (HFG) (E) on SARS-CoV-2 pseudoviral infection. Data are mean ± SEM (n = 3–6 biologically independent samples). F, G SARS-CoV-2 pseudoviral infection of primary human bronchial epithelial cells in the presence of increasing concentrations of HHT (F) and HFG (G). Data are mean ± SEM (n = 3 biologically independent samples). H SARS-CoV-2 pseudoviral infection of Caco-2 cells transfected with DCAF1 siRNA along with HFG treatment (100 nM). Data are mean ± SEM (n = 6 biologically independent samples). I SARS-CoV-2 pseudoviral infection of Caco-2 cells transfected with TMPRSS2 WT or lysine mutant prior to HFG treatment (100 nM). All SARS-CoV-2 pseudoviral data is corrected to cell number as determined by CellTiter-Glo. Data are mean ± SEM (n = 6 biologically independent samples). P-values are shown for comparisons to 0 time point or control, or as indicated by one-way ANOVA with Dunnett’s test of multiple comparisons (F, G), or a two-way ANOVA with Tukey’s test of multiple comparisons (B, H, I).

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