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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.
Poeta, Marco; Cioffi, Valentina; Buccigrossi, Vittoria; Nanayakkara, Merlin; Baggieri, Melissa; Peltrini, Roberto; Amoresano, Angela; Magurano, Fabio; Guarino, Alfredo.
  • Poeta M; Pediatrics Division, Department of Translational Medical Science, University of Naples Federico II, 80138, Naples, Italy.
  • Cioffi V; Pediatrics Division, Department of Translational Medical Science, University of Naples Federico II, 80138, Naples, Italy.
  • Buccigrossi V; Pediatrics Division, Department of Translational Medical Science, University of Naples Federico II, 80138, Naples, Italy.
  • Nanayakkara M; Pediatrics Division, Department of Translational Medical Science, University of Naples Federico II, 80138, Naples, Italy.
  • Baggieri M; Department of Infectious Diseases, National Institute of Health, Rome, Italy.
  • Peltrini R; Department of Public Health, University of Naples Federico II, Naples, Italy.
  • Amoresano A; Department of Chemical Sciences, University of Naples Federico II, Naples, Italy.
  • Magurano F; Department of Infectious Diseases, National Institute of Health, Rome, Italy.
  • Guarino A; Pediatrics Division, Department of Translational Medical Science, University of Naples Federico II, 80138, Naples, Italy. alfguari@unina.it.
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)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Silicates / NF-kappa B p50 Subunit / Chemokine CXCL10 / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Clinical Practice Guide / Prognostic study Limits: Humans Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-01217-2

Full text: Available Collection: International databases Database: MEDLINE Main subject: Silicates / NF-kappa B p50 Subunit / Chemokine CXCL10 / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Clinical Practice Guide / Prognostic study Limits: Humans Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-01217-2