• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

SARS-CoV-2 刺突蛋白的 Y674-R685 区域与人α7 烟碱型乙酰胆碱受体的功能相互作用。

A Functional Interaction Between Y674-R685 Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor.

机构信息

Instituto de Investigaciones Bioquímicas de Bahía Blanca, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur-Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Camino La Carrindanga Km 7-8000, Bahía Blanca, Argentina.

Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.

出版信息

Mol Neurobiol. 2022 Oct;59(10):6076-6090. doi: 10.1007/s12035-022-02947-8. Epub 2022 Jul 20.

DOI:10.1007/s12035-022-02947-8
PMID:35859025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9299415/
Abstract

The α7 nicotinic acetylcholine receptor (nAChR) is present in neuronal and non-neuronal cells and has anti-inflammatory actions. Molecular dynamics simulations suggested that α7 nAChR interacts with a region of the SARS-CoV-2 spike protein (S), and a potential contribution of nAChRs to COVID-19 pathophysiology has been proposed. We applied whole-cell and single-channel recordings to determine whether a peptide corresponding to the Y674-R685 region of the S protein can directly affect α7 nAChR function. The S fragment exerts a dual effect on α7. It activates α7 nAChRs in the presence of positive allosteric modulators, in line with our previous molecular dynamics simulations showing favourable binding of this accessible region of the S protein to the nAChR agonist binding site. The S fragment also exerts a negative modulation of α7, which is evidenced by a profound concentration-dependent decrease in the durations of openings and activation episodes of potentiated channels and in the amplitude of macroscopic responses elicited by ACh. Our study identifies a potential functional interaction between α7 nAChR and a region of the S protein, thus providing molecular foundations for further exploring the involvement of nAChRs in COVID-19 pathophysiology.

摘要

α7 型烟碱型乙酰胆碱受体（nAChR）存在于神经元和非神经元细胞中，具有抗炎作用。分子动力学模拟表明，α7 nAChR 与 SARS-CoV-2 刺突蛋白（S）的一个区域相互作用，并且已经提出 nAChRs 可能对 COVID-19 病理生理学有贡献。我们应用全细胞和单通道记录来确定 S 蛋白的 Y674-R685 区域对应的肽是否可以直接影响 α7 nAChR 功能。S 片段对 α7 具有双重作用。它在正变构调节剂存在下激活 α7 nAChRs，这与我们之前的分子动力学模拟结果一致，表明 S 蛋白的这个可及区域与烟碱型乙酰胆碱受体激动剂结合位点有良好的结合。S 片段还对 α7 产生负调节作用，这表现在增强通道的开放和激活事件的持续时间以及 ACh 诱发的宏观反应幅度随着浓度的增加而明显减少。我们的研究确定了 α7 nAChR 和 S 蛋白的一个区域之间的潜在功能相互作用，从而为进一步探索 nAChRs 在 COVID-19 病理生理学中的作用提供了分子基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/277f87a97077/12035_2022_2947_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/1319c414de4c/12035_2022_2947_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/1b1023401927/12035_2022_2947_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/5f2ebe064f3f/12035_2022_2947_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/55d8810744c5/12035_2022_2947_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/c680a3c3adfa/12035_2022_2947_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/63ce5ebca2c8/12035_2022_2947_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/277f87a97077/12035_2022_2947_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/1319c414de4c/12035_2022_2947_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/1b1023401927/12035_2022_2947_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/5f2ebe064f3f/12035_2022_2947_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/55d8810744c5/12035_2022_2947_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/c680a3c3adfa/12035_2022_2947_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/63ce5ebca2c8/12035_2022_2947_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e3/9299415/277f87a97077/12035_2022_2947_Fig7_HTML.jpg

相似文献

1
A Functional Interaction Between Y674-R685 Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor.SARS-CoV-2 刺突蛋白的 Y674-R685 区域与人α7 烟碱型乙酰胆碱受体的功能相互作用。
Mol Neurobiol. 2022 Oct;59(10):6076-6090. doi: 10.1007/s12035-022-02947-8. Epub 2022 Jul 20.
2
A potential interaction between the SARS-CoV-2 spike protein and nicotinic acetylcholine receptors.SARS-CoV-2 刺突蛋白与烟碱型乙酰胆碱受体的潜在相互作用。
Biophys J. 2021 Mar 16;120(6):983-993. doi: 10.1016/j.bpj.2021.01.037. Epub 2021 Feb 18.
3
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors.模拟结果支持严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白与烟碱型乙酰胆碱受体之间的相互作用。
bioRxiv. 2020 Sep 14:2020.07.16.206680. doi: 10.1101/2020.07.16.206680.
4
SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine receptors.SARS-CoV-2 刺突蛋白胞外域靶向α7 型烟碱型乙酰胆碱受体。
J Biol Chem. 2023 May;299(5):104707. doi: 10.1016/j.jbc.2023.104707. Epub 2023 Apr 13.
5
The SARS-CoV-2 Virus and the Cholinergic System: Spike Protein Interaction with Human Nicotinic Acetylcholine Receptors and the Nicotinic Agonist Varenicline.SARS-CoV-2 病毒与胆碱能系统：刺突蛋白与人烟碱型乙酰胆碱受体的相互作用及烟碱激动剂伐伦克林。
Int J Mol Sci. 2023 Mar 15;24(6):5597. doi: 10.3390/ijms24065597.
6
Nicotinic cholinergic system and COVID-19: In silico identification of interactions between α7 nicotinic acetylcholine receptor and the cryptic epitopes of SARS-Co-V and SARS-CoV-2 Spike glycoproteins.烟碱型乙酰胆碱能系统与 COVID-19：α7 型烟碱型乙酰胆碱受体与 SARS-CoV 和 SARS-CoV-2 刺突糖蛋白隐匿表位相互作用的计算鉴定。
Food Chem Toxicol. 2021 Mar;149:112009. doi: 10.1016/j.fct.2021.112009. Epub 2021 Jan 24.
7
SARS-Cov-2 spike protein fragment 674-685 protects mitochondria from releasing cytochrome c in response to apoptogenic influence.严重急性呼吸综合征冠状病毒2刺突蛋白片段674 - 685可保护线粒体免受凋亡诱导影响而释放细胞色素c。
Biochem Biophys Res Commun. 2021 Jul 5;561:14-18. doi: 10.1016/j.bbrc.2021.05.018. Epub 2021 May 11.
8
Agonists or positive allosteric modulators of α7 nicotinic acetylcholine receptor prevent interaction of SARS-Cov-2 receptor-binding domain with astrocytoma cells.α7 烟碱型乙酰胆碱受体激动剂或正变构调节剂可阻止 SARS-CoV-2 受体结合域与星形胶质细胞瘤的相互作用。
Biochem Biophys Res Commun. 2024 May 21;709:149825. doi: 10.1016/j.bbrc.2024.149825. Epub 2024 Mar 25.
9
Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications.烟碱型乙酰胆碱能系统与 COVID-19：SARS-CoV-2 与烟碱受体相互作用的计算鉴定及其潜在治疗靶点意义。
Int J Mol Sci. 2020 Aug 13;21(16):5807. doi: 10.3390/ijms21165807.
10
A human-specific, truncated α7 nicotinic receptor subunit assembles with full-length α7 and forms functional receptors with different stoichiometries.一种人类特异性的截断型α7 烟碱型乙酰胆碱受体亚基与全长 α7 组装，并形成具有不同计量比的功能性受体。
J Biol Chem. 2018 Jul 6;293(27):10707-10717. doi: 10.1074/jbc.RA117.001698. Epub 2018 May 21.

引用本文的文献

1
The Possible Mechanistic Basis of Individual Susceptibility to Spike Protein Injury.个体对刺突蛋白损伤易感性的可能机制基础。
Adv Virol. 2025 Jun 24;2025:7990876. doi: 10.1155/av/7990876. eCollection 2025.
2
Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike.糖基化的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白中脂肪酸位点的变构调节
Elife. 2025 Apr 10;13:RP97313. doi: 10.7554/eLife.97313.
3
Long COVID - a critical disruption of cholinergic neurotransmission?长期新冠——胆碱能神经传递的严重紊乱？

本文引用的文献

1
Could Small Neurotoxins-Peptides be Expressed during SARS-CoV-2 Infection?在新型冠状病毒感染期间会表达小神经毒素肽吗？
Curr Genomics. 2021 Dec 31;22(8):557-563. doi: 10.2174/1389202923666211221111527.
2
Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients.SARS-CoV-2 刺突蛋白在 COVID-19 患者尿液中的证据。
Kidney360. 2021 Apr 14;2(6):924-936. doi: 10.34067/KID.0002172021. eCollection 2021 Jun 24.
3
SARS-CoV-2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate.
Bioelectron Med. 2025 Feb 27;11(1):5. doi: 10.1186/s42234-025-00167-8.
4
Design, Synthesis, and Structure-Activity Relationships of Novel Peptide Derivatives of the Severe Acute Respiratory Syndrome-Coronavirus-2 Spike-Protein that Potently Inhibit Nicotinic Acetylcholine Receptors.新型严重急性呼吸综合征冠状病毒 2 刺突蛋白肽衍生物的设计、合成及构效关系研究，该衍生物能有效抑制烟碱型乙酰胆碱受体。
J Med Chem. 2024 Jun 13;67(11):9587-9598. doi: 10.1021/acs.jmedchem.4c00735. Epub 2024 May 30.
5
SARS-CoV-2-Related Olfactory Dysfunction: Autopsy Findings, Histopathology, and Evaluation of Viral RNA and ACE2 Expression in Olfactory Bulbs.与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）相关的嗅觉功能障碍：尸检结果、组织病理学以及嗅球中病毒RNA和血管紧张素转换酶2（ACE2）表达的评估
Biomedicines. 2024 Apr 9;12(4):830. doi: 10.3390/biomedicines12040830.
6
Cholinergic Polarization of Human Macrophages.人巨噬细胞的胆碱能极化。
Int J Mol Sci. 2023 Oct 29;24(21):15732. doi: 10.3390/ijms242115732.
7
Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers.“长新冠”中的心血管自主神经功能障碍：病理生理学、心率变异性和炎症标志物
Front Cardiovasc Med. 2023 Sep 1;10:1256512. doi: 10.3389/fcvm.2023.1256512. eCollection 2023.
8
SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine receptors.SARS-CoV-2 刺突蛋白胞外域靶向α7 型烟碱型乙酰胆碱受体。
J Biol Chem. 2023 May;299(5):104707. doi: 10.1016/j.jbc.2023.104707. Epub 2023 Apr 13.
9
α7- and α9-Containing Nicotinic Acetylcholine Receptors in the Functioning of Immune System and in Pain.α7- 和 α9- 型烟碱型乙酰胆碱受体在免疫系统功能和疼痛中的作用。
Int J Mol Sci. 2023 Mar 30;24(7):6524. doi: 10.3390/ijms24076524.
10
SARS-CoV-2 spike variants differ in their allosteric responses to linoleic acid.SARS-CoV-2 刺突变异体在对亚油酸的变构反应方面存在差异。
J Mol Cell Biol. 2023 Aug 3;15(3). doi: 10.1093/jmcb/mjad021.
SARS-CoV-2 刺突蛋白通过与肝素硫酸竞争结合导致血液凝结和血栓形成。
Int J Biol Macromol. 2021 Dec 15;193(Pt B):1124-1129. doi: 10.1016/j.ijbiomac.2021.10.112. Epub 2021 Oct 29.
4
Regulation of epithelial sodium channel activity by SARS-CoV-1 and SARS-CoV-2 proteins.SARS-CoV-1 和 SARS-CoV-2 蛋白对上皮钠离子通道活性的调节。
Biophys J. 2021 Jul 20;120(14):2805-2813. doi: 10.1016/j.bpj.2021.06.005. Epub 2021 Jun 29.
5
Structure and gating mechanism of the α7 nicotinic acetylcholine receptor.α7 型烟碱型乙酰胆碱受体的结构与门控机制。
Cell. 2021 Apr 15;184(8):2121-2134.e13. doi: 10.1016/j.cell.2021.02.049. Epub 2021 Mar 17.
6
A potential interaction between the SARS-CoV-2 spike protein and nicotinic acetylcholine receptors.SARS-CoV-2 刺突蛋白与烟碱型乙酰胆碱受体的潜在相互作用。
Biophys J. 2021 Mar 16;120(6):983-993. doi: 10.1016/j.bpj.2021.01.037. Epub 2021 Feb 18.
7
A conserved arginine with non-conserved function is a key determinant of agonist selectivity in α7 nicotinic ACh receptors.在α7 型烟碱型乙酰胆碱受体中，具有非保守功能的保守精氨酸是激动剂选择性的关键决定因素。
Br J Pharmacol. 2021 Apr;178(7):1651-1668. doi: 10.1111/bph.15389. Epub 2021 Feb 27.
8
Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein.超越屏蔽作用：聚糖在新冠病毒刺突蛋白中的作用
ACS Cent Sci. 2020 Oct 28;6(10):1722-1734. doi: 10.1021/acscentsci.0c01056. Epub 2020 Sep 23.
9
Neuropilin-1 is a host factor for SARS-CoV-2 infection.神经纤毛蛋白 1 是 SARS-CoV-2 感染的宿主因子。
Science. 2020 Nov 13;370(6518):861-865. doi: 10.1126/science.abd3072. Epub 2020 Oct 20.
10
Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.神经纤毛蛋白-1 促进 SARS-CoV-2 细胞进入和感染性。
Science. 2020 Nov 13;370(6518):856-860. doi: 10.1126/science.abd2985. Epub 2020 Oct 20.