The Global Phosphorylation Landscape of SARS-CoV-2 Infection
The Global Phosphorylation Landscape of SARS-CoV-2 Infection
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DOI：
10.1016/j.cell.2020.06.034
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发表时间：
2020-08-06
期刊：
影响因子：
64.5
通讯作者：
Krogan, Nevan J.
中科院分区：
文献类型：
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作者：
Bouhaddou, Mehdi;Memon, Danish;Krogan, Nevan J.
2019年冠状病毒病（COVID-19）大流行的病原体严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）已在全球感染了数百万人，并导致数十万人死亡，这凸显了开发抗病毒疗法的迫切需要。在这里，我们提出了一个定量质谱为基础的磷酸蛋白质组学调查SARS冠状病毒-2感染Vero E6细胞，揭示了戏剧性的重新布线的磷酸化对宿主和病毒蛋白。SARS-CoV-2感染促进酪蛋白激酶II（CK 2）和p38 MAPK激活，产生多种细胞因子，并关闭有丝分裂激酶，导致细胞周期停滞。感染也刺激了一个显着的诱导CK 2含有丝状伪足突起拥有出芽病毒颗粒。通过将全球磷酸化概况映射到失调的激酶和途径，鉴定了87种药物和化合物。我们发现p38、CK 2、CDK、AXL和PIKFYVE激酶的药理学抑制具有抗病毒功效，代表了潜在的COVID-19疗法。
The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.