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Sci Rep ; 11(1): 21725, 2021 11 05.
Article in English | MEDLINE | ID: covidwho-1504567

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.


Subject(s)
COVID-19/drug therapy , Chemokine CXCL10/metabolism , NF-kappa B p50 Subunit/metabolism , SARS-CoV-2 , Silicates/chemistry , Adsorption , Aluminum Compounds/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Anti-Inflammatory Agents , Binding Sites , Caco-2 Cells , Chromatography, Liquid , Clay , Diarrhea/etiology , Diarrhea/therapy , Enterocytes/metabolism , Gastroenterology , Humans , Magnesium Compounds/chemistry , Mass Spectrometry , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding/drug effects , Protein Domains , Rotavirus , Silicates/metabolism
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