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目的 通过比较严重急性呼吸综合征冠状病毒核衣壳蛋白（SARS-CoV-NP）和新型冠状病毒核衣壳蛋白（SARS-CoV-2-NP）与宿主蛋白互作差异，筛选出特异性差异蛋白，从蛋白质水平分析两者致病性差异。方法 蛋白下拉实验（pull-down）实验筛选与SARS-CoV-NP或SARS-CoV-2-NP相互作用的Vero细胞内的全部蛋白，质谱技术对筛选出的蛋白进行定性定量分析、蛋白功能注释和构建蛋白质-蛋白质相互作用（PPI）网络。结果 数据库检索得到1 345个蛋白。差异性分析显示，SARSCoV-NP组与SARS-CoV-2-NP组相比，下调差异蛋白数目为358个，上调差异蛋白数目为476个。生信分析显示，这些蛋白主要定位于细胞质和细胞核中，参与生物过程调控、代谢过程的调节等生物过程，发挥着离子结合、核苷酸结合和碳水化合物衍生物结合等分子功能，与新陈代谢和遗传信息处理等相关疾病的发生和发展密切相关，普遍含有RNA识别基序，色氨酸-天冬氨酸重复序列（WD）域等功能性结构域。结论 SARS-CoV-NP组与SARS-CoV-2-NP组相比，存在多个差异宿主蛋白，为新型冠状病毒致病的分子机制和治疗靶点的研究提供了依据。
Abstract：Objective To compare the differences in the interactions with host proteins between severe acute respiratory syndrome coronavirus(SARS-CoV) nucleocapsid protein(NP) and SARS-CoV-2-NP, and to screen out specific differential proteins for analyzing the pathogenicity differences between the two at the protein level.Methods All proteins in Vero cells interacting with SARS-CoV-NP or SARS-CoV-2-NP were screened by the pull-down assay, and the screened proteins were analyzed by mass spectrometry for quantitative and qualitative analysis, protein function annotation, and protein-protein interaction(PPI) network construction by mass spectrometry.Results A total of 1 345 proteins were retrieved from the database. Compared with the SARS-CoV-2-NP group, the SARS-CoVNP group had 358 downregulated differentially expressed proteins and 476 upregulated differentially expressed proteins. Biosignature analysis revealed that these proteins were predominantly located in the cytoplasm and nucleus. They participated in biological processes such as regulation of biological processes and metabolic processes. Their molecular functions included ion-binding, nucleotide-binding, and carbohydrate derivative-binding. These proteins were closely associated with diseases linked to metabolism and genetic information processing. Many of them contained functional structural domains like RNA recognition motifs and tryptophan-aspartic acid repeat(WD) domains.Conclusion Compared with the SARS-CoV-NP group, the SARS-CoV-2-NP group exhibited multiple differential host proteins, providing a basis for investigating the molecular pathogenesis and therapeutic targets of SARS-CoV-2.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.08.003
中图分类号:R373.1
引用信息:
[1]李欣奕,孙绿茵,马竹萍,等.SARS-CoV与SARS-CoV-2 NP蛋白同宿主蛋白互作差异的分析[J].安徽医科大学学报,2026,61(08):1348-1354.DOI:10.19405/j.cnki.issn1000-1492.2026.08.003.
基金信息:
辽宁省科学技术计划项目（编号：2022-BS-320）; 大学生创新创业训练计划项目（编号：S202410160009）~~
2026-07-10
2026-07-10
2026-07-10