Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels

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...

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Autores principales:	Meichen Yan, Yuan Dong, Xuena Bo, Yong Cheng, Jinbo Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	angiotensin-converting enzyme 2 interferon-stimulated gene NF-κB signaling inflammatory cytokine storm clinical drugs Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b34177cf3b7b4625bcfd0e032c3f04c9
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spelling	oai:doaj.org-article:b34177cf3b7b4625bcfd0e032c3f04c92021-11-19T05:07:44ZLarge Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels1663-981210.3389/fphar.2021.771555https://doaj.org/article/b34177cf3b7b4625bcfd0e032c3f04c92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.771555/fullhttps://doaj.org/toc/1663-9812Coronaviruses 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.Meichen YanYuan DongXuena BoYong ChengJinbo ChengFrontiers Media S.A.articleangiotensin-converting enzyme 2interferon-stimulated geneNF-κB signalinginflammatory cytokine stormclinical drugsTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	angiotensin-converting enzyme 2 interferon-stimulated gene NF-κB signaling inflammatory cytokine storm clinical drugs Therapeutics. Pharmacology RM1-950
spellingShingle	angiotensin-converting enzyme 2 interferon-stimulated gene NF-κB signaling inflammatory cytokine storm clinical drugs Therapeutics. Pharmacology RM1-950 Meichen Yan Yuan Dong Xuena Bo Yong Cheng Jinbo Cheng Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels
description	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.
format	article
author	Meichen Yan Yuan Dong Xuena Bo Yong Cheng Jinbo Cheng
author_facet	Meichen Yan Yuan Dong Xuena Bo Yong Cheng Jinbo Cheng
author_sort	Meichen Yan
title	Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels
title_short	Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels
title_full	Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels
title_fullStr	Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels
title_full_unstemmed	Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels
title_sort	large screening identifies ace2 positively correlates with nf-κb signaling activity and targeting nf-κb signaling drugs suppress ace2 levels
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b34177cf3b7b4625bcfd0e032c3f04c9
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Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels

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