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

Tanimoto, K., Hirota, K., Fukazawa, T., et al. Inhibits SARS-CoV-2 infection in invitro by suppressing its receptor, angiotensin-converting enzyme 2, via aryl hydrocarbon receptor signaling. SCI Rep 11, 16629 (2021). https://doi.org/10.1038/s41598-021-96109-w

Commentary

To understand the molecular mechanisms of SARS-CoV-2 infection, this study focused on the ACE2-mediated internalization mechanism of SARS-CoV-2.

Cigarette smoke is generally considered harmful and is also recognized as an etiological agent of COVID-19.

However, we found that cigarette smoke extract (CSE) treatment, surprisingly, suppressed ACE2 expression in HepG2 cells.

Therefore, we were investigating the mechanism of the effect of CSE on the expression of ACE2 in mammalian cells.

RNA-seq analysis suggested an inhibitory effect on ACE2, which may be inversely correlated with the induction of genes regulated by the aryl hydrocarbon receptor (AHR). We tested the AHR agonists 6-formylindolo(3,2-b)carbazole (FICZ) and omeprazole (OMP) to evaluate whether these treatments affect ACE2 expression.

Results showed that both FICZ and OMP clearly suppressed ACE2 expression in a dose-dependent manner, along with induction of CYP1A1.

Knockdown experiments showed a decrease in ACE2 with FICZ treatment in an AHR-dependent manner.

AHR agonist treatment inhibited SARS-CoV-2 infection of VeroE6 cells, as determined by immunoblotting analysis detecting SARS-CoV-2 specific nucleocapsid proteins.

They say that the study results show that treatment with AHR agonists such as FICZ and OMP reduces ACE2 expression through AHR activation and inhibits SARS-CoV-2 infection in mammalian cells.