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10.1016/j.jaci.2021.11.019

http://scihub22266oqcxt.onion/10.1016/j.jaci.2021.11.019
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34902435!8660661!34902435
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suck abstract from ncbi


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pmid34902435      J+Allergy+Clin+Immunol 2022 ; 149 (3): 923-933.e6
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  • The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression #MMPMID34902435
  • Pivniouk V; Pivniouk O; DeVries A; Uhrlaub JL; Michael A; Pivniouk D; VanLinden SR; Conway MY; Hahn S; Malone SP; Ezeh P; Churko JM; Anderson D; Kraft M; Nikolich-Zugich J; Vercelli D
  • J Allergy Clin Immunol 2022[Mar]; 149 (3): 923-933.e6 PMID34902435show ga
  • BACKGROUND: Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions. OBJECTIVES: We sought to investigate whether and how OM-85 treatment protects nonhuman primate and human epithelial cells against SARS-CoV-2. METHODS: ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung, and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro. RESULTS: OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein-pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation. CONCLUSIONS: OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of coronavirus disease 2019.
  • |Adjuvants, Immunologic/*administration & dosage[MESH]
  • |Angiotensin-Converting Enzyme 2/antagonists & inhibitors/genetics/immunology[MESH]
  • |Animals[MESH]
  • |COVID-19/immunology/*prevention & control/virology[MESH]
  • |Caco-2 Cells[MESH]
  • |Cell Extracts/*administration & dosage/immunology[MESH]
  • |Cells, Cultured[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Down-Regulation/drug effects[MESH]
  • |Epithelial Cells/drug effects/immunology/virology[MESH]
  • |HEK293 Cells[MESH]
  • |Host Microbial Interactions/drug effects/immunology[MESH]
  • |Humans[MESH]
  • |In Vitro Techniques[MESH]
  • |Lung/drug effects/immunology/virology[MESH]
  • |Mice[MESH]
  • |Mice, Inbred BALB C[MESH]
  • |Receptors, Virus/*antagonists & inhibitors/*immunology[MESH]
  • |SARS-CoV-2/*immunology[MESH]
  • |Serine Endopeptidases/drug effects/genetics/immunology[MESH]
  • |Transcription, Genetic/drug effects/immunology[MESH]


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