小柯机器人

研究绘制新冠病毒感染引起的全局性蛋白磷酸化图谱
2020-06-30 17:30
来源：小柯机器人

美国QBI COVID-19研究小组绘制了新冠病毒（ SARS-CoV-2）感染引起的全局性蛋白磷酸化图谱。这一研究成果于2020年6月28日在线发表在《细胞》上。

研究人员报道了Vero E6细胞中SARS-CoV-2感染的质谱定量蛋白质组学研究，从而揭示了宿主和病毒蛋白上磷酸化的显著变化。SARS-CoV-2感染促进了酪蛋白激酶II（CK2）和p38 MAP激酶的活化、多种细胞因子的产生以及有丝分裂激酶的抑制，从而导致细胞周期停滞。感染还明显诱导了包含CK2的丝状伪足凸起，这能够加工病毒颗粒。
 
通过将总体磷酸化谱图映射到失调的激酶和途径，研究人员鉴定出了87种药物和化合物。研究人员发现p38、CK2、CDK、AXL和PIKFYVE激酶的药理抑制作用具有抗病毒功效，这可能是潜在的COVID-19疗法。
 
附：英文原文

Title: The Global Phosphorylation Landscape of SARS-CoV-2 Infection

Author: Mehdi Bouhaddou, Danish Memon, Bjoern Meyer, Kris M. White, Veronica V. Rezelj, Miguel C. Marrero, Benjamin J. Polacco, James E. Melnyk, Svenja Ulferts, Robyn M. Kaake, Jyoti Batra, Alicia L. Richards, Erica Stevenson, David E. Gordon, Ajda Rojc, Kirsten Obernier, Jacqueline M. Fabius, Margaret Soucheray, Lisa Miorin, Elena Moreno, Cassandra Koh, Quang Dinh Tran, Alexandra Hardy, Rémy Robinot, Thomas Vallet, Benjamin E. Nilsson-Payant, Claudia Hernandez-Armenta, Alistair Dunham, Sebastian Weigang, Julian Knerr, Maya Modak, Diego Quintero, Yuan Zhou, Aurelien Dugourd, Alberto Valdeolivas, Trupti Patil, Qiongyu Li, Ruth Hüttenhain, Merve Cakir, Monita Muralidharan, Minkyu Kim, Gwendolyn Jang

Issue&Volume: 2020-06-28

Abstract: 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 MAP kinase activation, production of diverse cytokines, and shutdown of mitotic kinases resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodia 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 p38, CK2, CDKs, AXL and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.

DOI: 10.1016/j.cell.2020.06.034

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30811-4

Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：66.85
官方网址：https://www.cell.com/
投稿链接：https://www.editorialmanager.com/cell/default.aspx

本期文章：《细胞》：Online/在线发表

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