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多层次蛋白质组学揭示SARS-CoV-2和SARS-CoV对宿主的干扰
2021-04-15 11:52

德国慕尼黑工业大学Andreas Pichlmair小组利用多层次蛋白质组学揭示了SARS-CoV-2和SARS-CoV对宿主的干扰。2021年4月12日,《自然》杂志在线发表了这一研究成果。

研究人员同时进行了SARS-CoV-2和SARS-CoV的多组学研究。使用最先进的蛋白质组学,研究人员对两种病毒的相互作用组以及它们对源自肺的人类细胞系中转录组、蛋白质组、泛素组和磷酸化蛋白质组的影响进行了分析。然后将这些数据投射到细胞相互作用的全球网络上,揭示了SARS-CoV-2和SARS-CoV感染在不同层发生的扰动之间的串扰,并确定了这些密切相关的冠状病毒的独特且共同的分子机制。

众所周知,其参与组织纤维化的TGF-β途径被SARS-CoV-2 ORF8影响而失调,而被SARS-CoV-2 ORF3影响而发生自噬。广泛的数据集(可在https://covinet.innatelab.org获得)突出显示了许多可被现有药物靶向的热点,并且可以指导病毒和宿主导向疗法的合理设计,研究人员通过鉴定可以有效靶向SARS-CoV-2的激酶和MMP抑制剂来进行了举例说明。

据介绍,SARS-CoV-2的全球传播迫切需要对病毒蛋白的分子功能及其与宿主蛋白质组的相互作用的深入了解。几个单独的组学研究扩展了人们对COVID-19病理生理学的认识。此类数据集的集成能够获得病毒-宿主相互作用的整体视角,并定义SARS-CoV-2的致病特性(这受到实验系统异质性的限制)。

附:英文原文

Title: Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

Author: Alexey Stukalov, Virginie Girault, Vincent Grass, Ozge Karayel, Valter Bergant, Christian Urban, Darya A. Haas, Yiqi Huang, Lila Oubraham, Anqi Wang, M. Sabri Hamad, Antonio Piras, Fynn M. Hansen, Maria C. Tanzer, Igor Paron, Luca Zinzula, Thomas Enghleitner, Maria Reinecke, Teresa M. Lavacca, Rosina Ehmann, Roman Wlfel, Jrg Jores, Bernhard Kuster, Ulrike Protzer, Roland Rad, John Ziebuhr, Volker Thiel, Pietro Scaturro, Matthias Mann, Andreas Pichlmair

Issue&Volume: 2021-04-12

Abstract: The global emergence of SARS-CoV-2 urgently requires an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1–10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. We therefore conducted a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactome of both viruses, as well as their influence on transcriptome, proteome, ubiquitinome and phosphoproteome in a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon SARS-CoV-2 and SARS-CoV infections at different layers and identified unique and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org) highlights many hotspots that can be targeted by existing drugs and it can guide rational design of virus- and host-directed therapies, which we exemplify by identifying kinase and MMPs inhibitors with potent antiviral effects against SARS-CoV-2.

DOI: 10.1038/s41586-021-03493-4

Source: https://www.nature.com/articles/s41586-021-03493-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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