Inhibiting SARS-CoV-2 infection in vitro by suppressing its receptor, angiotensin-converting enzyme 2, via aryl-hydrocarbon receptor signal

Abstract Since understanding molecular mechanisms of SARS-CoV-2 infection is extremely important for developing effective therapies against COVID-19, we focused on the internalization mechanism via ACE2. Although cigarette smoke generally believed to be harmful pathogenesis extract (CSE) treatments were surprisingly found suppress expression ACE2 in HepG2 cells. We thus tried clarify CSE effects mammalian Because RNA-seq analysis suggested that suppressive might inversely correlated with induction genes regulated by aryl hydrocarbon receptor (AHR), AHR agonists 6-formylindolo(3,2-b)carbazole (FICZ) and omeprazole (OMP) tested assess whether those affected expression. Both FICZ OMP clearly suppressed a dose-dependent manner along inducing CYP1A1 . Knock-down experiments indicated reduction treatment an AHR-dependent manner. Finally, inhibited into Vero E6 cells as determined immunoblotting analyses detecting specific nucleocapsid protein. here demonstrate agonists, including FICZ, OMP, decreases activation, resulting suppression