Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.

Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.
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DOI:
10.1016/j.chom.2020.12.009
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发表时间:
2021-02-10
影响因子:
30.3
通讯作者:
Rice CM
Rice CM
中科院分区:
医学1区
文献类型:
--
作者:
Hoffmann HH;Sánchez-Rivera FJ;Schneider WM;Luna JM;Soto-Feliciano YM;Ashbrook AW;Le Pen J;Leal AA;Ricardo-Lax I;Michailidis E;Hao Y;Stenzel AF;Peace A;Zuber J;Allis CD;Lowe SW;MacDonald MR;Poirier JT;Rice CM

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持续的严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)大流行摧毁了全球经济,夺去了170多万人的生命,构成了一场紧迫的全球卫生危机。为了确定SARS-CoV-2和季节性冠状病毒感染所需的宿主因子,我们设计了一个集中的高覆盖率CRISPR-Cas9文库,靶向最近发表的SARS-CoV-2蛋白相互作用组的332个成员。我们利用该文库的紧凑性,在两种生理相关温度下系统地筛选SARS-CoV-2沿着三种相关冠状病毒(人冠状病毒229 E [HCoV-229 E],HCoV-NL 63和HCoV-OC 43),使我们能够以比基因组规模研究高得多的分辨率探测这种相互作用组。这种方法产生了一些见解,包括Rab GT3需求和糖基磷脂酰肌醇(GPI)锚生物合成的潜在病毒特异性差异,以及参与胆固醇稳态的多种泛冠状病毒因子的鉴定。该冠状病毒必要性目录可以为正在进行的药物开发工作提供信息,旨在拦截和治疗2019冠状病毒病(COVID-19),并帮助为未来的冠状病毒爆发做好准备。Hoffmann et al.使用定制的CRISPR文库来确定这些相互作用的宿主蛋白中哪些是SARS-CoV-2病毒以及三种季节性冠状病毒感染所必需的。这些因素代表了抗击COVID-19以及未来冠状病毒爆发的潜在目标。
The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has devastated the global economy and claimed more than 1.7 million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen SARS-CoV-2 at two physiologically relevant temperatures along with three related coronaviruses (human coronavirus 229E [HCoV-229E], HCoV-NL63, and HCoV-OC43), allowing us to probe this interactome at a much higher resolution than genome-scale studies. This approach yielded several insights, including potential virus-specific differences in Rab GTPase requirements and glycosylphosphatidylinositol (GPI) anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating coronavirus disease 2019 (COVID-19) and help prepare for future coronavirus outbreaks. Building upon a published SARS-CoV-2 protein interactome, Hoffmann et al. use a custom CRISPR library to determine which of these interacting host proteins are essential for infection by SARS-CoV-2 virus as well as three seasonal coronaviruses. These factors represent potential targets to combat COVID-19 and perhaps future coronavirus outbreaks.
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影响因子: --
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发表时间: 2021-01-07
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影响因子: 64.5
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