Genome-scale CRISPR screens identify host factors that promote human coronavirus infection.
Genome-scale CRISPR screens identify host factors that promote human coronavirus infection.
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DOI：
10.1186/s13073-022-01013-1
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发表时间：
2022-01-27
期刊：
影响因子：
12.3
通讯作者：
Norris MH
中科院分区：
文献类型：
--
作者：
Grodzki M;Bluhm AP;Schaefer M;Tagmount A;Russo M;Sobh A;Rafiee R;Vulpe CD;Karst SM;Norris MH
截至二零二一年十二月，COVID-19疫情已导致2. 75亿人感染及540万人死亡。虽然全球正在施用有效的疫苗，但由于抗原性新颖的SARS-CoV-2变体继续在地球仪各地出现，因此仍然非常需要抗病毒疗法。病毒在其生命周期的每一步都需要宿主因子，这为抗病毒药物设计提供了丰富的候选靶点。为了鉴定促进SARS-CoV-2感染的宿主因子，其具有跨冠状病毒家族的广谱活性的潜力，我们在两种细胞系（Vero E6和HEK 293 T异位表达ACE 2）中进行了基因组规模的CRISPR敲除筛选，其中含有SARS-CoV-2和引起普通感冒的人类冠状病毒OC 43。在Vero、HEK 293和人类小气道上皮细胞中进行基因敲除、CRISPR敲除和小分子测试，以验证我们的发现。虽然我们确定了先前报道的促进人类冠状病毒复制的多个基因和功能途径，但我们还确定了大量新的基因和途径。创建网站https://sarscrisprscreens.epi.ufl.edu/是为了以统一分析的方式对SARS-CoV 2 CRISPR屏幕进行可视化和比较。值得注意的是，在我们的筛选中富集了参与细胞周期调控的宿主因子，以及程序性mRNA衰变途径的几个关键组分。EDC 4和XRN 1在人小气道上皮细胞中冠状病毒复制中的作用得到验证。最后，我们确定了新的候选抗病毒化合物，靶向我们的筛选揭示的一些因素。总的来说，我们的研究证实并扩展了越来越多的文献，这些文献专注于了解关键的人类冠状病毒-宿主细胞相互作用，并利用这些知识进行合理的抗病毒药物开发。在线版本包含补充材料，可通过10.1186/s13073-022-01013-1获得。
The COVID-19 pandemic has resulted in 275 million infections and 5.4 million deaths as of December 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as antigenically novel SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design. To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we performed genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. Gene knockdown, CRISPR knockout, and small molecule testing in Vero, HEK293, and human small airway epithelial cells were used to verify our findings. While we identified multiple genes and functional pathways that have been previously reported to promote human coronavirus replication, we also identified a substantial number of novel genes and pathways. The website https://sarscrisprscreens.epi.ufl.edu/ was created to allow visualization and comparison of SARS-CoV2 CRISPR screens in a uniformly analyzed way. Of note, host factors involved in cell cycle regulation were enriched in our screens as were several key components of the programmed mRNA decay pathway. The role of EDC4 and XRN1 in coronavirus replication in human small airway epithelial cells was verified. Finally, we identified novel candidate antiviral compounds targeting a number of factors revealed by our screens. Overall, our studies substantiate and expand the growing body of literature focused on understanding key human coronavirus-host cell interactions and exploit that knowledge for rational antiviral drug development. The online version contains supplementary material available at 10.1186/s13073-022-01013-1.
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影响因子：
3.7
作者：
Gao, Huixin;Lin, Yuxia;Zhang, Ping
通讯作者：
Zhang, Ping
影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE
影响因子：
64.5
作者：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
β-核心就是使用溶酶体进行出口，而不是生物合成分泌途径。
影响因子：
64.5
作者：
Ghosh S;Dellibovi-Ragheb TA;Kerviel A;Pak E;Qiu Q;Fisher M;Takvorian PM;Bleck C;Hsu VW;Fehr AR;Perlman S;Achar SR;Straus MR;Whittaker GR;de Haan CAM;Kehrl J;Altan-Bonnet G;Altan-Bonnet N
通讯作者：
Altan-Bonnet N