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

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 cultured and prepared for a large PlateSeq drugs perturbational screening (10 96-well plates, 441 FDA-approved drugs in total)