Title: | "Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion" |
Author(s): | Poeta M; Cioffi V; Buccigrossi V; Nanayakkara M; Baggieri M; Peltrini R; Amoresano A; Magurano F; Guarino A; |
Address: | "Pediatrics Division, Department of Translational Medical Science, University of Naples Federico II, 80138, Naples, Italy. Department of Infectious Diseases, National Institute of Health, Rome, Italy. Department of Public Health, University of Naples Federico II, Naples, Italy. Department of Chemical Sciences, University of Naples Federico II, Naples, Italy. Pediatrics Division, Department of Translational Medical Science, University of Naples Federico II, 80138, Naples, Italy. alfguari@unina.it" |
DOI: | 10.1038/s41598-021-01217-2 |
ISSN/ISBN: | 2045-2322 (Electronic) 2045-2322 (Linking) |
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" |
Keywords: | "Adsorption Aluminum Compounds/chemistry Angiotensin-Converting Enzyme 2/metabolism Anti-Inflammatory Agents Binding Sites Caco-2 Cells Chemokine CXCL10/*metabolism Chromatography, Liquid Clay Diarrhea/etiology/therapy Enterocytes/metabolism Gastroenterolo;" |
Notes: | "MedlinePoeta, Marco Cioffi, Valentina Buccigrossi, Vittoria Nanayakkara, Merlin Baggieri, Melissa Peltrini, Roberto Amoresano, Angela Magurano, Fabio Guarino, Alfredo eng Research Support, Non-U.S. Gov't England 2021/11/07 Sci Rep. 2021 Nov 5; 11(1):21725. doi: 10.1038/s41598-021-01217-2" |