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 Overall design: 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)