Abstract
In clinical studies, OM-85 Broncho-Vaxom®, 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 (p < 0.001), TMPRSS2 (p < 0.001), DPP4 (p < 0.005), and cellular heparan sulfate (p < 0.01), while ADAM17 (p < 0.02) expression was significantly upregulated. Furthermore, OM-85 increased the level of sACE2 (p < 0.05), hyaluronic acid (p < 0.002), and hyaluronan synthase 1 (p < 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.
Highlights
Epithelial cells of the oral cavity, nasal duct, and upper airway are the primary targets for SARS-CoV-2 [1,2,3], by the interaction of the viral spike protein (S-protein) with the human angiotensin converting enzyme 2 (ACE2) and other host proteins and glycosaminoglycans [4,5]
This study investigated the effect of OM-85 on primary and immortalized human bronchial epithelial cells, and assessed the expression of all the above-mentioned proteins and GAG that affect the interaction of SARS-CoV-2 with ACE2
The expression of the SARS-CoV-2 interacting human host proteins (ACE2, transmembrane protease serine subtype 2 (TMPRSS2), dipeptidyl peptidase-4 (DPP4), and a disintegrin and metalloprotease 17 (ADAM17)) were analyzed in two immortalized human bronchial epithelial cell lines (BEAS-2B and Nuli) and four primary human bronchial epithelial cells isolated from patients without chronic inflammatory lung diseases
Summary
Epithelial cells of the oral cavity, nasal duct, and upper airway are the primary targets for SARS-CoV-2 [1,2,3], by the interaction of the viral spike protein (S-protein) with the human angiotensin converting enzyme 2 (ACE2) and other host proteins and glycosaminoglycans [4,5]. A recent study defined the susceptibility to SARS-CoV-2 infection as the result of a combination between the genetic variations of SARS-CoV-2 and the genetics of the host [6]. This implies that the different genetic variants of the viral. ACE2 is constitutively expressed on the cell membrane of respiratory tract epithelial cells and helps the SARS-CoV-2 to bind and infect. The generation of sACE2 is mainly controlled by the activity of ADAM17 (a disintergrin and metalloproteinase 17), which is expressed on the membrane of epithelial cells [8,9]. Diabetes, or obesity present the major risk group for COVID-19 and are characterized by high levels
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