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10.1038/s41598-021-96109-w

http://scihub22266oqcxt.onion/10.1038/s41598-021-96109-w
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suck abstract from ncbi


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pmid34404832      Sci+Rep 2021 ; 11 (1): 16629
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  • Inhibiting SARS-CoV-2 infection in vitro by suppressing its receptor, angiotensin-converting enzyme 2, via aryl-hydrocarbon receptor signal #MMPMID34404832
  • Tanimoto K; Hirota K; Fukazawa T; Matsuo Y; Nomura T; Tanuza N; Hirohashi N; Bono H; Sakaguchi T
  • Sci Rep 2021[Aug]; 11 (1): 16629 PMID34404832show ga
  • 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.
  • |*COVID-19 Drug Treatment[MESH]
  • |Angiotensin-Converting Enzyme 2/*antagonists & inhibitors/genetics/metabolism[MESH]
  • |Animals[MESH]
  • |Basic Helix-Loop-Helix Transcription Factors/*agonists/metabolism[MESH]
  • |COVID-19/virology[MESH]
  • |Carbazoles/*pharmacology/therapeutic use[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Cytochrome P-450 CYP1A1/metabolism[MESH]
  • |Dose-Response Relationship, Drug[MESH]
  • |Drug Evaluation, Preclinical[MESH]
  • |Gene Expression Regulation/drug effects[MESH]
  • |Gene Knockdown Techniques[MESH]
  • |Hep G2 Cells[MESH]
  • |Humans[MESH]
  • |Omeprazole/*pharmacology/therapeutic use[MESH]
  • |RNA-Seq[MESH]
  • |Receptors, Aryl Hydrocarbon/*agonists/metabolism[MESH]
  • |SARS-CoV-2/drug effects/pathogenicity[MESH]
  • |Signal Transduction/drug effects[MESH]
  • |Vero Cells[MESH]


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