Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Int J Mol Sci. 2023 Jun 29;24(13):10837. doi: 10.3390/ijms241310837.
Lung surfactant is a complex mixture of phospholipids and surfactant proteins that is produced in alveolar type 2 cells. It prevents lung collapse by reducing surface tension and is involved in innate immunity. Exogenous animal-derived and, more recently, synthetic lung surfactant has shown clinical efficacy in surfactant-deficient premature infants and in critically ill patients with acute respiratory distress syndrome (ARDS), such as those with severe COVID-19 disease. COVID-19 pneumonia is initiated by the binding of the viral receptor-binding domain (RBD) of SARS-CoV-2 to the cellular receptor angiotensin-converting enzyme 2 (ACE2). Inflammation and tissue damage then lead to loss and dysfunction of surface activity that can be relieved by treatment with an exogenous lung surfactant. Surfactant protein B (SP-B) is pivotal for surfactant activity and has anti-inflammatory effects. Here, we study the binding of two synthetic SP-B peptide mimics, Super Mini-B (SMB) and B-YL, to a recombinant human ACE2 receptor protein construct using molecular docking and surface plasmon resonance (SPR) to evaluate their potential as antiviral drugs. The SPR measurements confirmed that both the SMB and B-YL peptides bind to the rhACE2 receptor with affinities like that of the viral RBD-ACE2 complex. These findings suggest that synthetic lung surfactant peptide mimics can act as competitive inhibitors of the binding of viral RBD to the ACE2 receptor.
肺表面活性剂是一种复杂的磷脂和表面活性蛋白混合物，由肺泡 II 型细胞产生。它通过降低表面张力来防止肺塌陷，并参与固有免疫。外源性动物源性和最近的合成肺表面活性剂已在表面活性物质缺乏的早产儿和急性呼吸窘迫综合征（ARDS）等重症患者中显示出临床疗效，如严重 COVID-19 疾病患者。COVID-19 肺炎是由 SARS-CoV-2 的病毒受体结合域（RBD）与细胞受体血管紧张素转换酶 2（ACE2）结合引发的。随后的炎症和组织损伤导致表面活性物质的丧失和功能障碍，外源性肺表面活性剂的治疗可以缓解这种情况。表面活性蛋白 B（SP-B）对表面活性物质至关重要，具有抗炎作用。在这里，我们使用分子对接和表面等离子体共振（SPR）研究了两种合成 SP-B 肽模拟物 Super Mini-B（SMB）和 B-YL 与重组人 ACE2 受体蛋白构建体的结合，以评估它们作为抗病毒药物的潜力。SPR 测量结果证实，SMB 和 B-YL 肽都与 rhACE2 受体具有亲和力，类似于病毒 RBD-ACE2 复合物。这些发现表明，合成肺表面活性剂肽模拟物可以作为病毒 RBD 与 ACE2 受体结合的竞争性抑制剂。
