aluminum-magnesium-silicate and Diarrhea

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.

Topics: Adsorption; Aluminum Compounds; Angiotensin-Converting Enzyme 2; Anti-Inflammatory Agents; Binding Sites; Caco-2 Cells; Chemokine CXCL10; Chromatography, Liquid; Clay; COVID-19 Drug Treatment; Diarrhea; Enterocytes; Gastroenterology; Humans; Magnesium Compounds; Mass Spectrometry; Molecular Docking Simulation; Molecular Dynamics Simulation; NF-kappa B p50 Subunit; Protein Binding; Protein Domains; Rotavirus; SARS-CoV-2; Silicates

Smektit was used for treatment of 24 patients, incl. 10 hospitalized with diarrhoea of a non-infectious etiology (postoperative period, non-adherence to the dietetic regime). Microbiological examination involved only examination of the common flora of the large bowel. In the 10 hospitalized patients the complaints receded very rapidly, after a maximum of three days. In the remaining 14 patients who had resections on account of colorectal carcinoma the diarrhoea was in the majority due to reduction of the large bowel and thus reduction of the resorption area. The condition of ten patients became stabilized and the frequency of bowel movements decreased. In the group of four patients after subtotal colectomy only one patient improved. In three patients smektit administration had no effect. In these patients the cause of frequent bowel movements was the extensive reduction of the large bowel.

Topics: Adult; Aged; Aged, 80 and over; Aluminum Compounds; Colectomy; Colorectal Neoplasms; Diarrhea; Female; Humans; Magnesium Compounds; Male; Middle Aged; Postoperative Complications; Silicates