Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion

Abstract SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gas...

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Auteurs principaux:	Marco Poeta, Valentina Cioffi, Vittoria Buccigrossi, Merlin Nanayakkara, Melissa Baggieri, Roberto Peltrini, Angela Amoresano, Fabio Magurano, Alfredo Guarino
Format:	article
Langue:	EN
Publié:	Nature Portfolio 2021
Sujets:	Medicine R Science Q
Accès en ligne:	https://doaj.org/article/ad76c4a29c3840a2b7ebb4273137b8a4
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spelling	oai:doaj.org-article:ad76c4a29c3840a2b7ebb4273137b8a42021-11-08T10:55:36ZDiosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion10.1038/s41598-021-01217-22045-2322https://doaj.org/article/ad76c4a29c3840a2b7ebb4273137b8a42021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01217-2https://doaj.org/toc/2045-2322Abstract SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gastrointestinal (GI) tract. Diosmectite, an aluminomagnesium silicate adsorbent clay with antidiarrheal effects, is recommended in some COVID-19 management protocols. In rotavirus models, diosmectite prevents pathogenic effects by binding the virus and its enterotoxin. We tested the trapping and anti-inflammatory properties of diosmectite in a SARS-CoV-2 model. Trapping effects were tested in Caco-2 cells using spike protein receptor-binding domain (RBD) and heat-inactivated SARS-CoV-2 preparations. Trapping was assessed by immunofluorescence, alone or in the presence of cells. The effect of diosmectite on nuclear factor kappa B (NF-kappaB) activation and CXCL10 secretion induced by the spike protein RBD and heat-inactivated SARS-CoV-2 were analyzed by Western blot and ELISA, respectively. Diosmectite bound the spike protein RBD and SARS-CoV-2 preparation, and inhibited interaction of the spike protein RBD with ACE2 receptors on the Caco-2 cell surface. Diosmectite exposure also inhibited NF-kappaB activation and CXCL10 secretion. These data provide direct evidence that diosmectite can bind SARS-CoV-2 components and inhibit downstream inflammation, supporting a mechanistic rationale for consideration of diosmectite as a management option for COVID-19-associated diarrhea.Marco PoetaValentina CioffiVittoria BuccigrossiMerlin NanayakkaraMelissa BaggieriRoberto PeltriniAngela AmoresanoFabio MaguranoAlfredo GuarinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marco Poeta Valentina Cioffi Vittoria Buccigrossi Merlin Nanayakkara Melissa Baggieri Roberto Peltrini Angela Amoresano Fabio Magurano Alfredo Guarino Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion
description	Abstract SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gastrointestinal (GI) tract. Diosmectite, an aluminomagnesium silicate adsorbent clay with antidiarrheal effects, is recommended in some COVID-19 management protocols. In rotavirus models, diosmectite prevents pathogenic effects by binding the virus and its enterotoxin. We tested the trapping and anti-inflammatory properties of diosmectite in a SARS-CoV-2 model. Trapping effects were tested in Caco-2 cells using spike protein receptor-binding domain (RBD) and heat-inactivated SARS-CoV-2 preparations. Trapping was assessed by immunofluorescence, alone or in the presence of cells. The effect of diosmectite on nuclear factor kappa B (NF-kappaB) activation and CXCL10 secretion induced by the spike protein RBD and heat-inactivated SARS-CoV-2 were analyzed by Western blot and ELISA, respectively. Diosmectite bound the spike protein RBD and SARS-CoV-2 preparation, and inhibited interaction of the spike protein RBD with ACE2 receptors on the Caco-2 cell surface. Diosmectite exposure also inhibited NF-kappaB activation and CXCL10 secretion. These data provide direct evidence that diosmectite can bind SARS-CoV-2 components and inhibit downstream inflammation, supporting a mechanistic rationale for consideration of diosmectite as a management option for COVID-19-associated diarrhea.
format	article
author	Marco Poeta Valentina Cioffi Vittoria Buccigrossi Merlin Nanayakkara Melissa Baggieri Roberto Peltrini Angela Amoresano Fabio Magurano Alfredo Guarino
author_facet	Marco Poeta Valentina Cioffi Vittoria Buccigrossi Merlin Nanayakkara Melissa Baggieri Roberto Peltrini Angela Amoresano Fabio Magurano Alfredo Guarino
author_sort	Marco Poeta
title	Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion
title_short	Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion
title_full	Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion
title_fullStr	Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion
title_full_unstemmed	Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion
title_sort	diosmectite inhibits the interaction between sars-cov-2 and human enterocytes by trapping viral particles, thereby preventing nf-kappab activation and cxcl10 secretion
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ad76c4a29c3840a2b7ebb4273137b8a4
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Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion

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