Large Screening Identifies ACE2 Positively Correlates With NF-kappaB Signaling Activity and Targeting NF-kappaB Signaling Drugs Suppress ACE2 Levels #MMPMID34867400
Yan M; Dong Y; Bo X; Cheng Y; Cheng J
Front Pharmacol 2021[]; 12 (ä): 771555 PMID34867400show ga
Coronaviruses SARS-CoV-2 infected more than 156 million people and caused over 3 million death in the whole world, therefore a better understanding of the underlying pathogenic mechanism and the searching for more effective treatments were urgently needed. Angiotensin-converting enzyme 2 (ACE2) was the receptor for SARS-CoV-2 infection. In this study, we found that ACE2 was an interferon-stimulated gene (ISG) in human cell lines. By performing an ISG library screening, we found that ACE2 levels were positively regulated by multiple ISGs. Interestingly, ACE2 levels were highly correlated with ISGs-induced NF-kappaB activities, but not IFNbeta levels. Furthermore, using an approved clinical durgs library, we found two clinical drugs, Cepharanthine and Glucosamine, significantly inhibited ACE2 level, IFNbeta level, and NF-kappaB signaling downstream TNFalpha and IL6 levels. Our finding suggested the possible inhibitory effects of Cepharanthine and Glucosamine during SARS-CoV-2 infection and the subsequent inflammatory cytokine storm.