Abstract
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-κB activities, but not IFNβ levels. Furthermore, using an approved clinical durgs library, we found two clinical drugs, Cepharanthine and Glucosamine, significantly inhibited ACE2 level, IFNβ level, and NF-κB signaling downstream TNFα 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.
Highlights
The pathogenic coronaviruses including SARS, MERS and new SARS-CoV-2 are cross-species transmitted from animal to human
For the in vitro characteristic study of human Angiotensin-converting enzyme 2 (ACE2), human cell lines BEAS-2B cells and HMC3 cells were stimulated with IFNβ, viral RNA mimic poly(I:C) or viral DNA mimic poly(dA:dT) as indicated
We found that treatments of IFNβ, viral RNA mimic poly(I:C) and viral DNA mimic poly(dA:dT) signifcantly increased ACE2 mRNA levels in BEAS-2B cells (Figure 1A), along with significant enhancement of IFNβ, TNFα and IL6 levels (Figures 1B–D)
Summary
The pathogenic coronaviruses including SARS, MERS and new SARS-CoV-2 are cross-species transmitted from animal to human. SARS-CoV-2 infection causes severe respiratory syndrome, recent studies showed that SARS-CoV-2 infection affects central nervous system (Abboud et al, 2020; Iadecola et al, 2020; Massad et al, 2020; Teng et al, 2020; Wang et al, 2021). Due to the high transmission level, SARS-CoV-2 have infected over 156 million people and caused over 3 million death globally. Multiple evidences reveals the increased level of ACE2 in COVID-19 patients (Zhuang et al, 2020; Pinto et al, 2020; Liu et al, 2021). Reduced risk of severe COVID-19 symptom is found associated with patients that
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