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CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells.
Wang, Ke; Chen, Wei; Zhang, Zheng; Deng, Yongqiang; Lian, Jian-Qi; Du, Peng; Wei, Ding; Zhang, Yang; Sun, Xiu-Xuan; Gong, Li; Yang, Xu; He, Lei; Zhang, Lei; Yang, Zhiwei; Geng, Jie-Jie; Chen, Ruo; Zhang, Hai; Wang, Bin; Zhu, Yu-Meng; Nan, Gang; Jiang, Jian-Li; Li, Ling; Wu, Jiao; Lin, Peng; Huang, Wan; Xie, Liangzhi; Zheng, Zhao-Hui; Zhang, Kui; Miao, Jin-Lin; Cui, Hong-Yong; Huang, Min; Zhang, Jun; Fu, Ling; Yang, Xiang-Min; Zhao, Zhongpeng; Sun, Shihui; Gu, Hongjing; Wang, Zhe; Wang, Chun-Fu; Lu, Yacheng; Liu, Ying-Ying; Wang, Qing-Yi; Bian, Huijie; Zhu, Ping; Chen, Zhi-Nan.
  • Wang K; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Chen W; Beijing Institute of Biotechnology, Beijing, 100071, China.
  • Zhang Z; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Deng Y; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  • Lian JQ; Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • Du P; Beijing Institute of Biotechnology, Beijing, 100071, China.
  • Wei D; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Zhang Y; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Sun XX; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Gong L; Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • Yang X; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • He L; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  • Zhang L; MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University, Xi'an, 710049, China.
  • Yang Z; MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University, Xi'an, 710049, China.
  • Geng JJ; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Chen R; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Zhang H; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Wang B; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Zhu YM; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Nan G; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Jiang JL; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Li L; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Wu J; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Lin P; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Huang W; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Xie L; Sino Biological Inc., Beijing, 100176, China.
  • Zheng ZH; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
  • Zhang K; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
  • Miao JL; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Cui HY; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Huang M; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Zhang J; Beijing Institute of Biotechnology, Beijing, 100071, China.
  • Fu L; Beijing Institute of Biotechnology, Beijing, 100071, China.
  • Yang XM; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Zhao Z; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  • Sun S; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  • Gu H; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  • Wang Z; School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
  • Wang CF; Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • Lu Y; School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
  • Liu YY; School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
  • Wang QY; School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
  • Bian H; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China. hjbian@fmmu.edu.cn.
  • Zhu P; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. zhuping@fmmu.edu.cn.
  • Chen ZN; National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China. znchen@fmmu.edu.cn.
Signal Transduct Target Ther ; 5(1): 283, 2020 12 04.
Article in English | MEDLINE | ID: covidwho-957563
ABSTRACT
In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Basigin / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2020 Document Type: Article Affiliation country: S41392-020-00426-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Basigin / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2020 Document Type: Article Affiliation country: S41392-020-00426-x