Saxifraga stolonifera inhibits porcine epidemic diarrhea virus infection by disrupting nucleocapsid protein-p53 interaction.

IF 4.8 2区 医学 Q2 IMMUNOLOGY
Frontiers in Cellular and Infection Microbiology Pub Date : 2025-07-09 eCollection Date: 2025-01-01 DOI:10.3389/fcimb.2025.1615300
Hongde Lu, Haoyang Liu, Ning Guo, Yu Zhou, Haiyan Lu, Zhiyuan He, Hong Dong
{"title":"<i>Saxifraga stolonifera</i> inhibits porcine epidemic diarrhea virus infection by disrupting nucleocapsid protein-p53 interaction.","authors":"Hongde Lu, Haoyang Liu, Ning Guo, Yu Zhou, Haiyan Lu, Zhiyuan He, Hong Dong","doi":"10.3389/fcimb.2025.1615300","DOIUrl":null,"url":null,"abstract":"<p><p>Porcine epidemic diarrhea (PED) is an acute, highly contagious intestinal disease caused by the porcine epidemic diarrhea virus (PEDV), which has devastating effects on the global swine industry. Currently, no effective therapeutic agents have been identified for treating PEDV infections. <i>Saxifraga stolonifera</i> (<i>S. stolonifera</i>), valued in traditional Chinese medicine for its anti-inflammatory properties, remains poorly studied regarding its efficacy against PEDV. This study demonstrated the dose-dependent inhibition of PEDV nucleocapsid expression by <i>S. stolonifera in vitro</i>. <i>S. stolonifera</i> strongly inhibited the expression levels of pro-inflammatory cytokines. Using the network pharmacology, key components such as gallic acid, quercetin, coumarin, and caffeic acid were identified. KEGG pathway enrichment analysis revealed that <i>S. stolonifera</i> mainly targeted pathways including p53, MAPK, and TNF to exert anti-PEDV effects. <i>S. stolonifera</i> treatment disrupted the interaction of PEDV N protein and p53. It also modulated the p53-DREAM signaling pathway by reducing p53 and p21 protein levels, while enhancing p130 (Ser672) phosphorylation, E2F4, and Cyclin A protein expression levels. Molecular docking revealed stable hydrogen bonding between the seven core components and the PEDV N protein, with quercetin exhibiting the lowest binding energy. Amino acid sequence analysis showed that quercetin and other components share conserved binding sites with the PEDV N protein. These findings underscore the potential of <i>S. stolonifera</i> as a natural antiviral agent against PEDV infection.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1615300"},"PeriodicalIF":4.8000,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283740/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cellular and Infection Microbiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fcimb.2025.1615300","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Porcine epidemic diarrhea (PED) is an acute, highly contagious intestinal disease caused by the porcine epidemic diarrhea virus (PEDV), which has devastating effects on the global swine industry. Currently, no effective therapeutic agents have been identified for treating PEDV infections. Saxifraga stolonifera (S. stolonifera), valued in traditional Chinese medicine for its anti-inflammatory properties, remains poorly studied regarding its efficacy against PEDV. This study demonstrated the dose-dependent inhibition of PEDV nucleocapsid expression by S. stolonifera in vitro. S. stolonifera strongly inhibited the expression levels of pro-inflammatory cytokines. Using the network pharmacology, key components such as gallic acid, quercetin, coumarin, and caffeic acid were identified. KEGG pathway enrichment analysis revealed that S. stolonifera mainly targeted pathways including p53, MAPK, and TNF to exert anti-PEDV effects. S. stolonifera treatment disrupted the interaction of PEDV N protein and p53. It also modulated the p53-DREAM signaling pathway by reducing p53 and p21 protein levels, while enhancing p130 (Ser672) phosphorylation, E2F4, and Cyclin A protein expression levels. Molecular docking revealed stable hydrogen bonding between the seven core components and the PEDV N protein, with quercetin exhibiting the lowest binding energy. Amino acid sequence analysis showed that quercetin and other components share conserved binding sites with the PEDV N protein. These findings underscore the potential of S. stolonifera as a natural antiviral agent against PEDV infection.

鹿茸通过破坏核衣壳蛋白-p53相互作用抑制猪流行性腹泻病毒感染。
猪流行性腹泻(PED)是由猪流行性腹泻病毒(PEDV)引起的一种急性高传染性肠道疾病,对全球养猪业造成了毁灭性的影响。目前,尚未发现治疗PEDV感染的有效药物。匍匐茎(S. stolonifera)因其抗炎特性而在中药中具有重要价值,但其对PEDV的疗效研究较少。本研究证实了匍匐茎对PEDV核衣壳蛋白表达的剂量依赖性抑制作用。匍匐茎强烈抑制促炎细胞因子的表达水平。利用网络药理学,鉴定了没食子酸、槲皮素、香豆素和咖啡酸等关键成分。KEGG通路富集分析显示,匍花主要靶向p53、MAPK、TNF等通路发挥抗pedv作用。stolonifera处理破坏了PEDV N蛋白与p53的相互作用。它还通过降低p53和p21蛋白水平,同时提高p130 (Ser672)磷酸化、E2F4和Cyclin A蛋白表达水平来调节p53- dream信号通路。分子对接发现7个核心组分与PEDV N蛋白之间存在稳定的氢键,其中槲皮素的结合能最低。氨基酸序列分析表明槲皮素等成分与PEDV N蛋白具有保守的结合位点。这些发现强调了匍匐茎作为抗PEDV感染的天然抗病毒药物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
7.90
自引率
7.00%
发文量
1817
审稿时长
14 weeks
期刊介绍: Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信