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.
【저자키워드】 ACE2, Spike protein, ADAM17, glycosaminoglycans, OM-85 Broncho-Vaxom, TMPRSS2, 【초록키워드】 COVID-19, SARS-CoV-2, therapy, Human, Infection, Proteins, protease, RT-PCR, ELISA, DPP4, Dipeptidyl peptidase-4, Protein, lentivirus, SARS-CoV-2 spike protein, spike-protein, Clinical studies, receptor, expression, Quantitative, binding, Bacterial, cellular, Interaction, S-protein, Concentration, epithelial cell, Serine, enzyme, host cell membrane, transmembrane, bronchial epithelial cells, western blotting, Modification, sACE2, Effect, Cell, significantly, investigated, reduced, treated, upregulated, reduce, bronchial epithelial cell, viral respiratory, was reduced, expression of SARS-CoV-2, were assessed, 【제목키워드】 SARS-CoV-2, Human, bronchial, lysate,