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Genome-wide CRISPR activation screen identifies candidate receptors for SARS-CoV-2 entry.
Zhu, Shiyou; Liu, Ying; Zhou, Zhuo; Zhang, Zhiying; Xiao, Xia; Liu, Zhiheng; Chen, Ang; Dong, Xiaojing; Tian, Feng; Chen, Shihua; Xu, Yiyuan; Wang, Chunhui; Li, Qiheng; Niu, Xuran; Pan, Qian; Du, Shuo; Xiao, Junyu; Wang, Jianwei; Wei, Wensheng.
  • Zhu S; 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,
  • Liu Y; 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,
  • Zhou Z; 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,
  • Zhang Z; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, 100871, China.
  • Xiao X; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
  • Liu Z; Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, 100871, China.
  • Chen A; 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, Beijing, 100730, China.
  • Dong X; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
  • Tian F; 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,
  • Chen S; 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,
  • Xu Y; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
  • Wang C; 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, Beijing, 100730, China.
  • Li Q; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
  • Niu X; 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,
  • Pan Q; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, 100871, China.
  • Du S; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
  • Xiao J; Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, 100871, China.
  • Wang J; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
  • Wei W; 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,
Sci China Life Sci ; 65(4): 701-717, 2022 04.
Article in English | MEDLINE | ID: covidwho-1371380
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Sci China Life Sci Journal subject: Biology / Science Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Sci China Life Sci Journal subject: Biology / Science Year: 2022 Document Type: Article