Fang Lei, Zhou Liang, Tamm Michael, Roth Michael
Pulmonary Cell Research, Department of Biomedicine & Internal Medicine, University Hospital Basel, CH-4031 Basel, Switzerland.
Biomedicines. 2021 Oct 26;9(11):1544. doi: 10.3390/biomedicines9111544.
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 ( < 0.001), TMPRSS2 ( < 0.001), DPP4 ( < 0.005), and cellular heparan sulfate ( < 0.01), while ADAM17 ( < 0.02) expression was significantly upregulated. Furthermore, OM-85 increased the level of sACE2 ( < 0.05), hyaluronic acid ( < 0.002), and hyaluronan synthase 1 ( < 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.
在临床研究中，细菌溶解产物OM-85 Broncho-Vaxom可减少病毒性呼吸道感染。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）对上皮细胞的感染取决于其刺突蛋白（S蛋白）与宿主细胞膜蛋白的相互作用。在本研究中，我们调查了OM-85对人支气管上皮细胞S蛋白结合蛋白表达的影响。人支气管上皮细胞用OM-85处理5天。通过蛋白质免疫印迹法和定量逆转录聚合酶链反应测定SARS-CoV-2受体血管紧张素转换酶2（ACE2）、跨膜蛋白酶丝氨酸2型（TMPRSS2）、二肽基肽酶4（DPP4）和去整合素和金属蛋白酶17（ADAM17）的表达。通过酶联免疫吸附测定法评估可溶性（s）ACE2、硫酸乙酰肝素、乙酰肝素酶和透明质酸。OM-85显著降低了ACE2（<0.001）、TMPRSS2（<0.001）、DPP4（<0.005）和细胞硫酸乙酰肝素（<0.01）的表达，而ADAM17（<0.02）的表达显著上调。此外，OM-85增加了sACE2（<0.05）、透明质酸（<0.002）和透明质酸合酶1（<0.01）的水平。因此，在用OM-85预处理的细胞中，SARS-CoV-2刺突蛋白假型慢病毒的感染减少。OM-85的所有作用均呈浓度和时间依赖性。结果表明，OM-85可能通过修饰宿主细胞膜蛋白和特定糖胺聚糖来减少SARS-CoV-2 S蛋白与上皮细胞的结合。因此，OM-85可被视为COVID-19治疗的附加药物。
