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 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.

Lacticaseibacillus rhamnosus GG Counteracts Rotavirus-Induced Ion Secretion and Enterocyte Damage by Inhibiting Oxidative Stress and Apoptosis Through Specific Effects of Living and Postbiotic Preparations

“…NF-kB activation has a key role in intestinal epithelial permeability ( Dominguez et al., 2013 ; Yang et al., 2014 ) as well as in infections ( Santoro et al., 2003 ), including RV ( Rossen et al., 2004 ) and SARS-CoV-2 ( Poeta et al., 2021 ) infections. NF-kB is found in the cytoplasm as an inactive factor, a heterodimer of p50 and p65 subunits bound with a member of the IkB inhibitor protein family.…”

Binding and inactivation of human coronaviruses, including SARS-CoV-2, onto purified clinoptilolite-tuff

“…In order to develop a material capable of widely neutralizing the increasing number of SARS-CoV-2 variants, it is important to find a substance which interacts with the virus in a relatively non-specific manner. In this regard, a few natural substances are currently investigated 8 , 14 , 32 , 33 .…”

“…An ideal antiviral substance would bind and/or inactivate all coronavirus variants independently of their mutations. Binding of viruses by mineral substances has already been demonstrated using sand and soil beds 11 , 12 , diatomaceous earth 13 , diosmectite 14 and clays 15 , 16 . Even though the binding mechanisms are unspecific, sorption may be so strong that only an insignificant proportion of the bound virus can effectively be desorbed 15 .…”

Spike S1 domain interactome in non-pulmonary systems: A role beyond the receptor recognition

“…Although COVID-19 mainly affects the respiratory tract, other organs have been identified as further SARS-CoV-2 targets, such as the kidneys and the gastrointestinal tract, leading to severe dysfunctions and damages ( Torjesen, 2021 ; Hunt et al, 2021 ). Indeed, both renal HK-2 and the adenocarcinoma colorectal Caco-2 cell lines have been reported to be infected by SARS-CoV-2 ( Yeung et al, 2021 ; Shuai et al, 2020 ), with inflammatory response mainly mediated by the S protein interaction with the cell surface, such as demonstrated in Caco-2 cell lines in terms of NFk-beta activation and CXCL10 secretion ( Poeta et al, 2021 ).…”