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小纤维神经自身抗原与人类冠状病毒抗原:是否存在分子模拟的可能性?

Autoantigens of Small Nerve Fibers and Human Coronavirus Antigens: Is There a Possibility for Molecular Mimicry?

机构信息

The Laboratory of the Mosaic of Autoimmunity and Department of Pathology, Saint Petersburg State University, 199034, Saint-Petersburg, Russia.

Saint Petersburg State University Hospital, 198103, Saint-Petersburg, Russia.

出版信息

Curr Microbiol. 2024 Sep 19;81(11):366. doi: 10.1007/s00284-024-03885-5.

Abstract

In post-COVID-19 syndrome, clinical presentation of the nerve fiber dysfunction plays an important role. The possibility of autoantigen cross-mimicry of human coronaviruses and the peripheral nervous system needs to be investigated. The bioinformatic analysis was applied to search for possible common protein sequences located in the immunoreactive epitopes. Among the autoantigens of the human nervous system, fibroblast growth factor receptor protein 3, myelin protein P0, myelin protein P2, sodium channel protein type 9, alpha protein subunit, plexin-D1 protein and ubiquitin-carboxyl-terminal hydrolase protein of the L1 isoenzyme were selected. The original "Alignmentaj" analytical program was created. The UniProt database, Protein Data Bank, and AlphaFold databases were used. The analysis of protein sequence similarities of spike glycoproteins in human coronaviruses revealed common pentapeptides of the MERS-CoV-2 virus with the fibroblast growth factor receptor 3 and myelin protein P2. Among seasonal coronaviruses, common peptide sequences were identified in HCoV-HKU-1 virus with sodium channel protein type 9 subunit alpha and Plexin-D1, HCoV-OC43 with Plexin-D1, as well as HCoV-NL63 with Plexin-D1 and Ubiquitin carboxyl-terminal hydrolase isozyme L1. Some shared peptides belong to immunoreactive epitopes. The most important targets for the molecular similarities are the sodium channel subunits and fibroblast growth factor receptor 3, both for seasonal and highly pathogenic coronaviruses. The data obtained make it possible to identify new potential targets for the development of autoimmune reactions that may occur against the background of the infections with highly pathogenic as well as seasonal coronaviruses.

摘要

在新冠病毒后综合征中,神经纤维功能障碍的临床表现起着重要作用。需要研究人类冠状病毒和周围神经系统之间的自身抗原交叉模拟的可能性。应用生物信息学分析来搜索位于免疫反应性表位的可能的共同蛋白序列。在人类神经系统的自身抗原中,选择了成纤维细胞生长因子受体蛋白 3、髓鞘蛋白 P0、髓鞘蛋白 P2、钠通道蛋白 9 型、α蛋白亚单位、神经丛蛋白 D1 蛋白和 L1 同工型的泛素羧基末端水解酶蛋白。创建了原始的“Alignmentaj”分析程序。使用了 UniProt 数据库、蛋白质数据库和 AlphaFold 数据库。对人类冠状病毒刺突糖蛋白的蛋白序列相似性分析显示,MERS-CoV-2 病毒与成纤维细胞生长因子受体 3 和髓鞘蛋白 P2 有共同的五肽。在季节性冠状病毒中,在 HCoV-HKU-1 病毒与钠通道蛋白 9 型α亚单位和神经丛蛋白 D1、HCoV-OC43 与神经丛蛋白 D1 以及 HCoV-NL63 与神经丛蛋白 D1 和泛素羧基末端水解酶同工型 L1 中都鉴定到了共同的肽序列。一些共同的肽属于免疫反应性表位。分子相似性的最重要的靶标是钠通道亚单位和成纤维细胞生长因子受体 3,它们既是季节性的也是高致病性的冠状病毒的重要靶标。所获得的数据使人们能够识别可能发生在高致病性和季节性冠状病毒感染背景下的自身免疫反应的新潜在靶标。

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