解码SARS-CoV-2和HCoV-OC43在COVID-19神经学表现中的共同分子机制：系统生物学方法

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-05-28 DOI:10.1016/j.genrep.2025.102269

Maryam Mozafar , Seyed Amir Mirmotalebisohi , Marzieh Sameni , Zeinab Dehghan , Hassan Zohrevand , Zargham Sepehrizadeh , Mohammad Ali Faramarzi , Ahmad Reza Shahverdi , Hakimeh Zali

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引用次数: 0

摘要

背景与目的随着COVID-19大流行在全球范围内的发展，出现了大量关于SARS-CoV-2神经学表现的报道。考虑到SARS-CoV-2和HCoV-OC43具有相似的神经侵袭作用和部分系统发育接近性，本研究探讨了它们之间共享的分子机制。我们旨在通过系统生物学方法增强对COVID-19神经表现的理解，解码介导SARS-CoV-2神经系统并发症的关键基因、生物过程和途径。方法利用来自基因表达Omnibus的高通量组学数据集（SARS-CoV-2的GSE174745和HCoV-OC43的GSE13879）。我们在Cytoscape中生成了蛋白质-蛋白质相互作用网络和MCODE集群。使用Fisher精确测试确定了两种感染之间的重要关系，并选择了关键的共享基因作为药物再利用的目标。Real-time PCR评估了一些关键基因的表达水平，DAVID和STRING数据库用于功能富集研究。结果介导COVID-19发病机制的共享富集通路包括神经退行性变、mTOR信号通路、TNF信号通路、补体和凝血级联以及细胞凋亡。我们的研究证实了神经covid患者中STAT1、YY1、ATF3、ATF4和DDIT3表达水平的变化，这些基因先前与其他病毒性神经系统疾病有关。在经验证对COVID-19呼吸系统并发症有效的再用途药物中，戊酸雌二醇、黄体酮、碘甲状腺原氨酸、螺内酯、吲哚美辛、阿司匹林和环孢素在控制COVID-19神经系统影响方面显示出潜在的治疗价值。结论这项经过验证的系统生物学研究，在基因表达分析的支持下，揭示了对理解COVID-19神经学方面至关重要的分子机制和相互作用。这些发现为未来的研究和潜在的治疗策略奠定了基础。

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Decoding shared molecular mechanisms of SARS-CoV-2 and HCoV-OC43 in COVID-19 neurological manifestations: a systems biology approach

Background and objectives

As the COVID-19 pandemic developed throughout the world, there were an excessive number of reports of SARS-CoV-2's neurological manifestations. This study investigated shared molecular mechanisms between SARS-CoV-2 and HCoV-OC43, considering their similar neuroinvasive effects and partial phylogenetic proximity. We aimed to enhance understanding of COVID-19 neural manifestations through a systems biology approach, decoding crucial genes, biological processes, and pathways to mediate SARS-CoV-2 neurological complications.

Methods

We utilized high-throughput omics datasets from the Gene Expression Omnibus (GSE174745 for SARS-CoV-2 and GSE13879 for HCoV-OC43). We generated protein-protein interaction networks and MCODE clusters in Cytoscape. Significant relationships between the two infections were identified using the Fisher exact test, and the critical shared genes were selected as targets for drug repurposing. Real-time PCR assessed the expression levels of some crucial genes, and DAVID and STRING databases were used for functional enrichment studies.

Results

Some shared enriched pathways mediating the COVID-19 pathogenesis included neurodegeneration, mTOR signaling, TNF signaling, complement and coagulation cascades, and Apoptosis. Our study confirmed changes in the expression levels of STAT1, YY1, ATF3, ATF4, and DDIT3 in neuro-COVID patients, with these genes previously implicated in other viral nervous system diseases. Among repurposed drugs with validated efficacy for respiratory complications of COVID-19, Estradiol valerate, Progesterone, Liothyronine, Spironolactone, Indomethacin, Aspirin, and Cyclosporine show potential therapeutic value for managing COVID-19's neurological effects.

Conclusion

This validated systems biology study, supported by gene expression analysis, unveils molecular mechanisms and interactions crucial for understanding the neurological aspects of COVID-19. These findings lay the groundwork for future research and potential therapeutic strategies.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.