Host–virus protein–protein interactions play key roles in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a comprehensive interactome study between the virus and host cells using tandem affinity purification and proximity-labeling strategies and identified 437 human proteins as the high-confidence interacting proteins. Further characterization of these interactions and comparison to other large-scale study of cellular responses to SARS-CoV-2 infection elucidated how distinct SARS-CoV-2 viral proteins participate in its life cycle. With these data mining, we discovered potential drug targets for the treatment of COVID-19. The interactomes of two key SARS-CoV-2-encoded viral proteins, NSP1 and N, were compared with the interactomes of their counterparts in other human coronaviruses. These comparisons not only revealed common host pathways these viruses manipulate for their survival, but also showed divergent protein–protein interactions that may explain differences in disease pathology. This comprehensive interactome of SARS-CoV-2 provides valuable resources for the understanding and treating of this disease.

中文翻译：

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SARS-CoV-2与人类冠状病毒的相互作用组揭示了可能影响发病机制的宿主因素

宿主-病毒蛋白质-蛋白质相互作用在严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的生命周期中起着关键作用。我们使用串联亲和纯化和邻近标记策略在病毒和宿主细胞之间进行了全面的相互作用组研究，并确定了 437 种人类蛋白质作为高可信度的相互作用蛋白质。进一步表征这些相互作用并与其他对 SARS-CoV-2 感染的细胞反应的大规模研究进行比较，阐明了不同的 SARS-CoV-2 病毒蛋白如何参与其生命周期。通过这些数据挖掘，我们发现了治疗 COVID-19 的潜在药物靶点。将 SARS-CoV-2 编码的两个关键病毒蛋白 NSP1 和 N 的相互作用组与其他人类冠状病毒中对应物的相互作用组进行了比较。这些比较不仅揭示了这些病毒为生存而操纵的共同宿主途径，而且还显示了不同的蛋白质 - 蛋白质相互作用，这可能解释了疾病病理学的差异。这种 SARS-CoV-2 的综合相互作用组为理解和治疗这种疾病提供了宝贵的资源。