Fig. 4: α₁AT inhibits SARS-CoV-2 replication in primary human airway cells.

a Small airway epithelial cells (SAECs) were treated with 100 µM of Prolastin (α₁AT, green) 1 h prior to, or 3 and 24 h post infection (hpi) with SARS-CoV-2 at a MOI of 1. 100 µM CM (blue) added 1 h prior to infection served as control. Immediately after the inoculum was removed (0 dpi) and at day 6 post infection, supernatants were harvested and subjected to RT-qPCR specific for SARS-CoV-2 ORF1b nsp14. Virus titers from day 0 were subtracted from titers at day 6. The means of technical duplicates of one experiment performed in triplicates are shown. b The apical and basal site of human airway epithelial cells (HAEC) grown at air–liquid interface was exposed to PBS, α₁AT (10 µM or 0.5 mg/ml) and remdesivir (5 µM) and then inoculated with SARS-CoV-2 (9.25 × 10² PFU) for 2 h. Cells were fixed at day 1, 2, and 3 post infection, stained with DAPI (cell nuclei, blue), a SARS-CoV-2 specific spike antibody (SARS-CoV-2 S, green) and an α-tubulin-specific antibody (red). Images shown are derived from one donor and represent maximum projections of serial sections along the basolateral to apical cell axis. Scale bar: 50 μm. c Number of infected cells per area in mock- (PBS, gray), α₁AT- (blue) or remdesivir-treated (green), SARS-CoV-2 infected HAECs. Values represent the mean number of infected HAECs from 2 donors at 5 random spots per culture, treatment and day ± SEM. Source data are provided as a Source Data file. For more images, see Supplementary Fig. 7.