Proteomics of SARS-CoV-2-infected host cells reveals therapy targets
Proteomics of SARS-CoV-2-infected host cells reveals therapy targets
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DOI：
10.1038/s41586-020-2332-7
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发表时间：
2020-05-14
期刊：
影响因子：
64.8
通讯作者：
Muench, Christian
中科院分区：
文献类型：
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作者：
Bojkova, Denisa;Klann, Kevin;Muench, Christian
最近发现了一种新的冠状病毒，并命名为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。人类感染SARS-CoV-2导致2019冠状病毒病（COVID-19），并已在地球仪迅速传播（1，2）。SARS-CoV-2显示出与其他冠状病毒的一些相似之处;然而，缺乏治疗选择和对SARS-CoV-2如何感染细胞的理解。在这里，我们确定了宿主细胞的途径，由SARS-CoV-2调制，并表明，这些途径的抑制，防止病毒在人类细胞中的复制。我们建立了一个人细胞培养模型感染的临床分离的SARS-CoV-2。使用这种细胞培养系统，我们通过translatome（3）和蛋白质组蛋白质组学确定了SARS-CoV-2在感染后不同时间的感染特征。这些分析表明，SARS-CoV-2重塑了中央细胞通路，如翻译，剪接，碳代谢，蛋白质稳态（蛋白质稳态）和核酸代谢。靶向这些途径的小分子抑制剂阻止了病毒在细胞中的复制。我们的研究结果揭示了SARS-CoV-2的细胞感染特征，并能够鉴定抑制病毒复制的药物。我们预计，我们的研究结果将指导努力，以了解与SARS-CoV-2感染后宿主细胞的调制的分子机制。此外，我们的发现为开发治疗COVID-19的疗法提供了见解。SARS-CoV-2调节人类细胞中的中心细胞通路，如翻译、剪接、碳代谢、蛋白质稳态和核酸代谢;这些通路可以被小分子抑制剂抑制，以防止病毒在细胞中复制。
A new coronavirus was recently discovered and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV-2 in humans causes coronavirus disease 2019 (COVID-19) and has been rapidly spreading around the globe(1,2). SARS-CoV-2 shows some similarities to other coronaviruses; however, treatment options and an understanding of how SARS-CoV-2 infects cells are lacking. Here we identify the host cell pathways that are modulated by SARS-CoV-2 and show that inhibition of these pathways prevents viral replication in human cells. We established a human cell-culture model for infection with a clinical isolate of SARS-CoV-2. Using this cell-culture system, we determined the infection profile of SARS-CoV-2 by translatome(3)and proteome proteomics at different times after infection. These analyses revealed that SARS-CoV-2 reshapes central cellular pathways such as translation, splicing, carbon metabolism, protein homeostasis (proteostasis) and nucleic acid metabolism. Small-molecule inhibitors that target these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and have enabled the identification of drugs that inhibit viral replication. We anticipate that our results will guide efforts to understand the molecular mechanisms that underlie the modulation of host cells after infection with SARS-CoV-2. Furthermore, our findings provide insights for the development of therapies for the treatment of COVID-19.SARS-CoV-2 modulates central cellular pathways, such as translation, splicing, carbon metabolism, proteostasis and nucleic acid metabolism, in human cells; these pathways can be inhibited by small-molecule inhibitors to prevent viral replication in the cells.