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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2021-10-01
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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 |
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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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