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

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

Ectopic ACTH syndrome revealed as severe hypokalemia and persistent hypertension during the perioperative period: a case report.

Both severe hypokalemia and persistent hypertension are clinical symptoms of hyperaldosteronism. Hyperaldosteronism may occur as a primary or secondary syndrome. Excess ACTH produced ectopically by tumors may induce hyperaldosteronism through the mineralocorticoid activity of glucocorticoids that are upregulated by ACTH. Licorice, with the active ingredient glycyrrhiza, is also a well-known inducer of hyperaldosteronism under specific conditions. In this report, we describe a case of severe hypokalemia caused by ectopic ACTH syndrome (EAS) elicited by an intrathoracic carcinoid tumor, which had transformed to produce ACTH during the 6-year clinical course, and was modulated by licorice ingestion. Hypokalemia was not clearly recognized preoperatively but became obvious within 3 h of general anesthesia with epidural blockade. At the end of anesthesia, arterial blood gas analysis indicated severe hypokalemia ([K(+)] = 1.7 mEq/l) and metabolic alkalosis (pH 7.56, PaCO(2) = 54.9 mmHg, HCO(3)(-) = 44.5 mmol/l, BE = 21.8 mmol/l), without any typical symptoms such as muscle weakness or ECG abnormalities. The hypokalemia was resistant to potassium supplementation and persisted for 4 days. Perioperative imbalance between the administration and elimination of potassium and surgical stress might contribute to the rapid exacerbation and induce the clinical manifestation of EAS.