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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Autores principales:	Lei Fang, Liang Zhou, Michael Tamm, Michael Roth
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	OM-85 Broncho-Vaxom ACE2 TMPRSS2 ADAM17 glycosaminoglycans spike protein Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ea0888db1ae94693a4a8d7c730fccc81
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spelling	oai:doaj.org-article:ea0888db1ae94693a4a8d7c730fccc812021-11-25T16:48:49ZOM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells10.3390/biomedicines91115442227-9059https://doaj.org/article/ea0888db1ae94693a4a8d7c730fccc812021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1544https://doaj.org/toc/2227-9059In 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.Lei FangLiang ZhouMichael TammMichael RothMDPI AGarticleOM-85 Broncho-VaxomACE2TMPRSS2ADAM17glycosaminoglycansspike proteinBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1544, p 1544 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	OM-85 Broncho-Vaxom ACE2 TMPRSS2 ADAM17 glycosaminoglycans spike protein Biology (General) QH301-705.5
spellingShingle	OM-85 Broncho-Vaxom ACE2 TMPRSS2 ADAM17 glycosaminoglycans spike protein Biology (General) QH301-705.5 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
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.
format	article
author	Lei Fang Liang Zhou Michael Tamm Michael Roth
author_facet	Lei Fang Liang Zhou Michael Tamm Michael Roth
author_sort	Lei Fang
title	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_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_sort	om-85 broncho-vaxom<sup>®</sup>, a bacterial lysate, reduces sars-cov-2 binding proteins on human bronchial epithelial cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ea0888db1ae94693a4a8d7c730fccc81
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OM-85 Broncho-Vaxom<sup>®</sup>, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells

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