Targeting invasion strategy of SARS-CoV-2 in bronchial epithelial cells

Abstract: "COVID19 is caused by the infection of airway epithelial cells and causes severe respiratory collapse that escalates in an overactivation of the immune system. Objectives: To identify the cellular mechanisms in primary epithelial cells in response to SARS-Cov2, the regulation of ACE2, pattern recognition receptors and host defense mechanisms. Further, to investigate the effect of IFN-g and IL-4 on epithelial infection and understand, which epithelial differentiation stages are susceptible to SARS-Cov2. Furthermore, we will investigate the role of potential therapeutic options to inhibit IFN-?-induced ACE2 expression using specific inhibitors for bradykinin-b2 receptor (Icatibant;HOE140), JAK/STAT-pathway (Tofacitinib), FoxO1 (AS1842856), as the ACE2 promoter contains IRF2 and FOXO1 binding sites.Preliminary Results: Primary human epithelial cells can differentiate into type-1 and type-2 epithelial cells affecting large proportions of the functional portfolio. We propose to identify the Sars-Cov2 secretion profile triggered in E1-differentiated cells, which could be used for home-care diagnostic kits, even if the viral origin is unknown. We discovered that ACE2, the SARS-Cov2 entry receptor is strongly up-regulated in the E1 cells. Furthermore, ACE2 protein was found to be higher in E1 cells, while Icatibant, a licensed drug, inhibits ACE2 up-regulation in E1 cells.Outlook: The proposed project sheds light epithelial immune response triggered by SARS-Cov2 in context of the E1 differentiation pathway and offers novel solutions for diagnosis and therapy."; Research Type: discovery; Study population: not applicable