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硒代蛋氨酸通过ROS介导的信号通路抑制呼吸道合胞病毒感染诱导的细胞凋亡和炎症反应。

Selenomethionine Inhibited RSV Infection-Induced Apoptosis and Inflammatory Response through ROS-Mediated Signaling Pathway.

作者信息

Li Chuqing, Wei Yuqun, Li Jiali, Lai Jia, Zeng Yuhui, Zhu Bing, Li Yinghua, Zhao Mingqi

机构信息

Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No 318 Renminzhong Road, Yuexiu, Guangzhou 510120, Guangdong, China.

出版信息

ACS Omega. 2025 Aug 28;10(35):40258-40270. doi: 10.1021/acsomega.5c05364. eCollection 2025 Sep 9.

Abstract

Respiratory syncytial virus (RSV) is the leading pathogen of acute lower respiratory tract infections in children under 5 years of age worldwide. Respiratory syncytial virus pneumonia in infants and children causes more deaths than influenza each year due to the high rate of severe illness. There is a lack of safe and effective antiviral drugs, and the development of novel antirespiratory syncytial virus drugs is of great clinical importance. Selenomethionine (SeMet), as the main ingredient in commercially available selenium supplements, exerts excellent antioxidant, antiviral, immunomodulatory, and other physiological functions mainly in the form of selenoprotein. The antiviral mechanism of SeMet anti-RSV was explored by detecting the apoptotic state, the degree of DNA damage, cytokine and reactive oxygen species (ROS) secretion levels, and the mitochondrial membrane potential. Meanwhile, this study screened the affinity of SeMet for common RSV target proteins and explored the dynamic interactions between SeMet and the screened viral target proteins.: SeMet inhibited apoptosis and inflammatory responses by regulating the ROS-mediated PARP/Bcl-2, NF-κB/JAK1-STAT3 signaling pathways. Meanwhile, SeMet formed a stable interaction with RSV polymerase and may bind to key amino acid residues of RSV polymerase mainly through hydrogen bonding.

摘要

呼吸道合胞病毒(RSV)是全球5岁以下儿童急性下呼吸道感染的主要病原体。由于重症发生率高,婴幼儿呼吸道合胞病毒肺炎每年导致的死亡人数比流感更多。目前缺乏安全有效的抗病毒药物,因此开发新型抗呼吸道合胞病毒药物具有重要的临床意义。硒代蛋氨酸(SeMet)作为市售硒补充剂的主要成分,主要以硒蛋白的形式发挥出色的抗氧化、抗病毒、免疫调节等生理功能。通过检测凋亡状态、DNA损伤程度、细胞因子和活性氧(ROS)分泌水平以及线粒体膜电位,探讨了SeMet抗RSV的抗病毒机制。同时,本研究筛选了SeMet对常见RSV靶蛋白的亲和力,并探讨了SeMet与筛选出的病毒靶蛋白之间的动态相互作用。SeMet通过调节ROS介导的PARP/Bcl-2、NF-κB/JAK1-STAT3信号通路抑制凋亡和炎症反应。同时,SeMet与RSV聚合酶形成稳定的相互作用,可能主要通过氢键与RSV聚合酶的关键氨基酸残基结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfd/12423889/06228567ace7/ao5c05364_0001.jpg

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