OM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells

In clinical studies, OM-85 Broncho-Vaxom<sup>®</sup>, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated th...

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Main Authors: Lei Fang, Liang Zhou, Michael Tamm, Michael Roth
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/9/11/1544
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author Lei Fang
Liang Zhou
Michael Tamm
Michael Roth
author_facet Lei Fang
Liang Zhou
Michael Tamm
Michael Roth
author_sort Lei Fang
collection DOAJ
description In clinical studies, OM-85 Broncho-Vaxom<sup>®</sup>, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated the effect of OM-85 on the expression of S-protein binding proteins by human bronchial epithelial cells. Human bronchial epithelial cells were treated with OM-85 over 5 days. The expression of SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2), transmembrane protease serine subtype 2 (TMPRSS2), dipeptidyl peptidase-4 (DPP4), and a disintegrin and metalloprotease 17 (ADAM17) were determined by Western blotting and quantitative RT-PCR. Soluble (s)ACE2, heparan sulfate, heparanase, and hyaluronic acid were assessed by ELISA. OM-85 significantly reduced the expression of ACE2 (<i>p</i> < 0.001), TMPRSS2 (<i>p</i> < 0.001), DPP4 (<i>p</i> < 0.005), and cellular heparan sulfate (<i>p</i> < 0.01), while ADAM17 (<i>p</i> < 0.02) expression was significantly upregulated. Furthermore, OM-85 increased the level of sACE2 (<i>p</i> < 0.05), hyaluronic acid (<i>p</i> < 0.002), and hyaluronan synthase 1 (<i>p</i> < 0.01). Consequently, the infection by a SARS-CoV-2 spike protein pseudo-typed lentivirus was reduced in cells pretreated with OM-85. All effects of OM-85 were concentration- and time-dependent. The results suggest that OM-85 might reduce the binding of SARS-CoV-2 S-protein to epithelial cells by modification of host cell membrane proteins and specific glycosaminoglycans. Thus, OM-85 might be considered as an add-on for COVID-19 therapy.
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spelling doaj.art-ea0888db1ae94693a4a8d7c730fccc812023-11-22T22:29:48ZengMDPI AGBiomedicines2227-90592021-10-01911154410.3390/biomedicines9111544OM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial CellsLei Fang0Liang Zhou1Michael Tamm2Michael Roth3Pulmonary Cell Research, Department of Biomedicine & Internal Medicine, University Hospital Basel, CH-4031 Basel, SwitzerlandPulmonary Cell Research, Department of Biomedicine & Internal Medicine, University Hospital Basel, CH-4031 Basel, SwitzerlandPulmonary Cell Research, Department of Biomedicine & Internal Medicine, University Hospital Basel, CH-4031 Basel, SwitzerlandPulmonary Cell Research, Department of Biomedicine & Internal Medicine, University Hospital Basel, CH-4031 Basel, SwitzerlandIn clinical studies, OM-85 Broncho-Vaxom<sup>®</sup>, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated the effect of OM-85 on the expression of S-protein binding proteins by human bronchial epithelial cells. Human bronchial epithelial cells were treated with OM-85 over 5 days. The expression of SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2), transmembrane protease serine subtype 2 (TMPRSS2), dipeptidyl peptidase-4 (DPP4), and a disintegrin and metalloprotease 17 (ADAM17) were determined by Western blotting and quantitative RT-PCR. Soluble (s)ACE2, heparan sulfate, heparanase, and hyaluronic acid were assessed by ELISA. OM-85 significantly reduced the expression of ACE2 (<i>p</i> < 0.001), TMPRSS2 (<i>p</i> < 0.001), DPP4 (<i>p</i> < 0.005), and cellular heparan sulfate (<i>p</i> < 0.01), while ADAM17 (<i>p</i> < 0.02) expression was significantly upregulated. Furthermore, OM-85 increased the level of sACE2 (<i>p</i> < 0.05), hyaluronic acid (<i>p</i> < 0.002), and hyaluronan synthase 1 (<i>p</i> < 0.01). Consequently, the infection by a SARS-CoV-2 spike protein pseudo-typed lentivirus was reduced in cells pretreated with OM-85. All effects of OM-85 were concentration- and time-dependent. The results suggest that OM-85 might reduce the binding of SARS-CoV-2 S-protein to epithelial cells by modification of host cell membrane proteins and specific glycosaminoglycans. Thus, OM-85 might be considered as an add-on for COVID-19 therapy.https://www.mdpi.com/2227-9059/9/11/1544OM-85 Broncho-VaxomACE2TMPRSS2ADAM17glycosaminoglycansspike protein
spellingShingle Lei Fang
Liang Zhou
Michael Tamm
Michael Roth
OM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells
Biomedicines
OM-85 Broncho-Vaxom
ACE2
TMPRSS2
ADAM17
glycosaminoglycans
spike protein
title OM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells
title_full OM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells
title_fullStr OM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells
title_full_unstemmed OM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells
title_short OM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells
title_sort om 85 broncho vaxom sup r sup a bacterial lysate reduces sars cov 2 binding proteins on human bronchial epithelial cells
topic OM-85 Broncho-Vaxom
ACE2
TMPRSS2
ADAM17
glycosaminoglycans
spike protein
url https://www.mdpi.com/2227-9059/9/11/1544
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AT michaeltamm om85bronchovaxomsupsupabacteriallysatereducessarscov2bindingproteinsonhumanbronchialepithelialcells
AT michaelroth om85bronchovaxomsupsupabacteriallysatereducessarscov2bindingproteinsonhumanbronchialepithelialcells