Division of Ophthalmology, Ümraniye Trn. And Rch. Hospital, Istanbul, Turkey.
Ophthalmology Department, University of Health Science, Derince Training and Research Hospital, Izmit-Kocaeli, Turkey.
Immunol Res. 2024 Feb;72(1):50-71. doi: 10.1007/s12026-023-09412-1. Epub 2023 Aug 29.
Thrombotic events associated with SARS-CoV-2 at the vascular endothelium still remains unclear. The aim of the current study is to determine the relationship between cellular proteins on the (ocular) vascular endothelial surface and the immune thrombotic and/or endotheliopathy process elicited by SARS-CoV-2 using an in-silico modeling. The structural S (spike glycoprotein), N (nucleocapsid protein), M (membrane protein), and E (envelope protein) proteins, an accessory protein (ORF1ab) of SARS-CoV-2 and 158 cellular proteins associated with retinal vascular endothelial cell surface or structure were included in this study for comparison of three-dimensional (3D) structure and sequence. Sixty-nine of the retinal proteins were obtained from the Uniprot database. Remaining proteins not included in the database were included in the study after they were converted into 3D structures using the RaptorX web tool. Sequence and three-dimensional structure of SARS-COV-2 S, N, M, E, ORF1ab proteins and retinal vascular endothelial proteins were compared with mTM-align server. Proteins with significant similarity (score above 0.5) were validated with the TM-align web server. Immune and thrombosis-related protein-receptor interactions of similar proteins was checked with CABS-dock. We detected a high level of structural similarity between E protein and ACE, ACE2, LAT1, and TM9SF4 endothelial proteins. In addition, PECAM-1 was found to be structurally similar to ORF1ab and S protein. When we evaluated the likelihood/potential to stimulate an immune responses/a cytokine release, TLR-2 and TLR-3, which are highly susceptible to SARS-CoV2, showed a potential receptor-protein interaction with retinal vascular endothelial proteins. Our study demonstrates that SARS-CoV-2 proteins may have structural similarities with vascular endothelial proteins, and therefore, as immunological target sites, the counterpart proteins on the endothelial surface of many organs may also be secondarily affected by any immune response against SARS-CoV-2 structural proteins.
血管内皮细胞与 SARS-CoV-2 相关的血栓形成事件仍不清楚。本研究旨在通过计算机模拟来确定 SARS-CoV-2 细胞表面蛋白与免疫血栓形成和/或内皮病变过程之间的关系。本研究纳入了 SARS-CoV-2 的结构蛋白 S（刺突糖蛋白）、N（核衣壳蛋白）、M（膜蛋白）和 E（包膜蛋白）、辅助蛋白 ORF1ab 和 158 种与视网膜血管内皮细胞表面或结构相关的细胞蛋白，用于比较三维（3D）结构和序列。69 种视网膜蛋白来自 Uniprot 数据库。数据库中未包含的其余蛋白在使用 RaptorX 网络工具转换为 3D 结构后包含在研究中。SARS-COV-2 S、N、M、E、ORF1ab 蛋白和视网膜血管内皮蛋白的序列和三维结构与 mTM-align 服务器进行了比较。使用 TM-align 网络服务器对具有显著相似性（得分高于 0.5）的蛋白进行了验证。使用 CABS-dock 检查了类似蛋白的免疫和血栓形成相关蛋白-受体相互作用。我们检测到 E 蛋白与 ACE、ACE2、LAT1 和 TM9SF4 内皮蛋白之间存在高度的结构相似性。此外，PECAM-1 与 ORF1ab 和 S 蛋白在结构上相似。当我们评估刺激免疫反应/细胞因子释放的可能性/潜力时，TLR-2 和 TLR-3 对 SARS-CoV2 高度敏感，与视网膜血管内皮蛋白表现出潜在的受体-蛋白相互作用。我们的研究表明，SARS-CoV-2 蛋白可能与血管内皮蛋白具有结构相似性，因此，作为免疫靶位点，许多器官内皮表面的对应蛋白也可能受到针对 SARS-CoV-2 结构蛋白的任何免疫反应的继发性影响。
