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典型文献
Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2
文献摘要:
Host cellular receptors play key roles in the determination of virus tropism and pathogenesis.However,little is known about SARS-CoV-2 host receptors with the exception of ACE2.Furthermore,ACE2 alone cannot explain the multi-organ tropism of SARS-CoV-2 nor the clinical differences between SARS-CoV-2 and SARS-CoV,suggesting the involvement of other receptor(s).Here,we performed genomic receptor profiling to screen 5054 human membrane proteins individually for interaction with the SARS-CoV-2 capsid spike (S) protein.Twelve proteins,including ACE2,ASGR1,and KREMEN1,were identified with diverse S-binding affinities and patterns.ASGR1 or KREMEN1 is sufficient for the entry of SARS-CoV-2 but not SARS-CoV in vitro and in vivo.SARS-CoV-2 utilizes distinct ACE2/ASGR1/KREMEN1 (ASK) receptor combinations to enter different cell types,and the expression of ASK together displays a markedly stronger correlation with Virus susceptibility than that of any individual receptor at both the cell and tissue levels.The cocktail of ASK-related neutralizing antibodies provides the most substantial blockage of SARS-CoV-2 infection in human lung organoids when compared to individual antibodies.Our study revealed an interacting host receptome of SARS-CoV-2,and identified ASGR1 and KREMEN1 as alternative functional receptors that play essential roles in ACE2-independent virus entry,providing insight into SARS-CoV-2 tropism and pathogenesis,as well as a community resource and potential therapeutic strategies for further COVID-19 investigations.
文献关键词:
作者姓名:
Yunqing Gu;Jun Cao;Xinyu Zhang;Hai Gao;Yuyan Wang;Jia Wang;Juan He;Xiaoyi Jiang;Jinlan Zhang;Guanghui Shen;Jie Yang;Xichen Zheng;Gaowei Hu;Yuanfei Zhu;Shujuan Du;Yunkai Zhu;Rong Zhang;Jianqing Xu;Fei Lan;Di Qu;Guoliang Xu;Yun Zhao;Dong Gao;Youhua Xie;Min Luo;Zhigang Lu
作者机构:
The Fifth People's Hospital of Shanghai,the Shanghai Key Laboratory of Medical Epigenetics,the International Co-laboratory of Medical Epigenetics and Metabolism,Ministry of Science and Technology,Institutes of Biomedical Sciences,Shanghai Institute of Infectious Diseases and Biosecurity,Shanghai Medical College,Fudan University,Shanghai,China;Institute of Pediatrics,Children's Hospital of Fudan University,Shanghai,China;Zhongshan-Xuhui Hospital,Fudan University,Shanghai,China;Key Laboratory of Medical Molecular Virology (MOE/MOH),School of Basic Medical Sciences,Shanghai Institute of Infectious Diseases and Biosecurity,Shanghai Medical College,Fudan University,Shanghai,China;State Key Laboratory of Molecular Biology,CAS Center for Excellence in Molecular Cell Science,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai,China;State Key Laboratory of Cell Biology,Shanghai Key Laboratory of Molecular Andrology,CAS Center for Excellence in Molecular Cell Science,institute of Biochemistry and Ceil Biology,Shanghai institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai,China;Shanghai Public Health Clinical Center,Fudan University,Shanghai,China
引用格式:
[1]Yunqing Gu;Jun Cao;Xinyu Zhang;Hai Gao;Yuyan Wang;Jia Wang;Juan He;Xiaoyi Jiang;Jinlan Zhang;Guanghui Shen;Jie Yang;Xichen Zheng;Gaowei Hu;Yuanfei Zhu;Shujuan Du;Yunkai Zhu;Rong Zhang;Jianqing Xu;Fei Lan;Di Qu;Guoliang Xu;Yun Zhao;Dong Gao;Youhua Xie;Min Luo;Zhigang Lu-.Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2)[J].细胞研究(英文版),2022(01):24-37
A类:
Receptome,KREMEN1,ASGR1,receptome
B类:
profiling,identifies,as,alternative,functional,receptors,SARS,CoV,Host,cellular,key,roles,determination,virus,tropism,pathogenesis,However,little,known,about,host,exception,ACE2,Furthermore,alone,cannot,explain,multi,nor,clinical,differences,between,suggesting,involvement,other,Here,performed,genomic,screen,human,membrane,proteins,individually,interaction,capsid,spike,Twelve,including,were,identified,diverse,binding,affinities,patterns,sufficient,entry,but,vitro,vivo,utilizes,distinct,ASK,combinations,enter,different,types,expression,together,displays,markedly,stronger,correlation,Virus,susceptibility,than,that,any,both,tissue,levels,cocktail,related,neutralizing,antibodies,provides,most,substantial,blockage,infection,lung,organoids,when,compared,Our,study,revealed,interacting,essential,independent,providing,insight,into,well,community,resource,potential,therapeutic,strategies,further,investigations
AB值:
0.50914
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