Identification and Targeting of Regulators of SARS-CoV-2-Host interactions in the Airway Epithelium [scRNA-Seq]

The conducting airway epithelium is the first line of defense in the respiratory tract against pathogens and a prime site of SARS-CoV-2 viral entry, serving to maintain a high viral load during lung infection. The impact of SARS-CoV-2 infection in the respiratory epithelium has been extensively studied. However, still less is known about the regulators of SARS-Cov-2-induced programs that facilitate infection and viral replication in distinct human airway epithelial cell populations, such as basal, secretory, and multiciliated cells. Here, we used SARS-CoV-2-infection of human airway epithelial organotypic cultures, single cell transcriptomics, large FDA-approved drug perturbation profiles combined with Master Regulator analysis to identify host cell defense and response pathways determinants of viral infection Primary human airway epithelial cells were isolated from de-identified adult human transplant organ donors and were grown in PnuemaCult ALI (media was changed every other day until day 21). ALI-differentiated cells at day 21 were inoculated on the apical surface by SARS- CoV-2 and were allowed to grow for 1, 3, and 6 days post infection (dpi), prior to be submitted for Single-Cell RNA Sequencing.