Genome-wide CRISPR activation screen identifies candidate receptors for SARS-CoV-2 entry  

作　　者：Shiyou Zhu Ying Liu Zhuo Zhou Zhiying Zhang Xia Xiao Zhiheng Liu Ang Chen Xiaojing Dong Feng Tian Shihua Chen Yiyuan Xu Chunhui Wang Qiheng Li Xuran Niu Qian Pan Shuo Du Junyu Xiao Jianwei Wang Wensheng Wei 

机构地区：[1]Biomedical Pioneering Innovation Center,Beijing Advanced Innovation Center for Genomics,Peking-Tsinghua Center for Life Sciences,Peking University Genome Editing Research Center,State Key Laboratory of Protein and Plant Gene Research,School of Life Sciences,Peking University,Beijing,100871,China [2]State Key Laboratory of Protein and Plant Gene Research,School of Life Sciences,Peking University,Peking-Tsinghua Center for Life Sciences,Peking University,Beijing Advanced Innovation Center for Genomics,Peking University,Beijing 100871,China [3]NHC Key Laboratory of Systems Biology of Pathogens and Christophe Merieux Laboratory,Institute of Pathogen Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Key Laboratory of Respiratory Disease Pathogenomics,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China [4]Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China

出　　处：《Science China(Life Sciences)》2022年第4期701-717,共17页中国科学（生命科学英文版）

基　　金：supported by funds from the National Key R&D Program of China (2020YFA0707800 to W.W., 2020YFA0707600 to Z.Z.);Beijing Municipal Science & Technology Commission (Z181100001318009);the National Natural Science Foundation of China (31930016);Beijing Advanced Innovation Center for Genomics at Peking University and the Peking-Tsinghua Center for Life Sciences (to W.W.);the National Natural Science Foundation of China (31870893);the National Major Science & Technology Project for Control and Prevention of Major Infectious Diseases in China (2018ZX10301401 to Z.Z.);China Postdoctoral Science Foundation (2020M670031 to Y.L.)

摘　　要：The outbreak of coronavirus disease 2019(COVID-19) caused by SARS-CoV-2 has created a global health crisis. SARS-CoV-2 infects varieties of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative viral entry pathways. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. Beyond known host proteins, i.e., ACE2, TMPRSS2, and NRP1, we identified multiple host components,among which LDLRAD3, TMEM30A, and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike’s N-terminal domain(NTD). Their essential and physiological roles have been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in an ACE2-independent fashion. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of COVID-19 countermeasures.

关 键 词：CRISPRa screen SARS-CoV-2 novel receptors 

分 类 号：Q78[生物学—分子生物学] R373[医药卫生—病原生物学]