2. Academic Validation
  3. CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

  • Signal Transduct Target Ther. 2020 Dec 4;5(1):283. doi: 10.1038/s41392-020-00426-x.
Ke Wang 1,  Wei Chen 2,  Zheng Zhang 1,  Yongqiang Deng 3,  Jian-Qi Lian 4,  Peng Du 2,  Ding Wei 1,  Yang Zhang 1,  Xiu-Xuan Sun 1,  Li Gong 4,  Xu Yang 1,  Lei He 3,  Lei Zhang 5,  Zhiwei Yang 5,  Jie-Jie Geng 1,  Ruo Chen 1,  Hai Zhang 1,  Bin Wang 1,  Yu-Meng Zhu 1,  Gang Nan 1,  Jian-Li Jiang 1,  Ling Li 1,  Jiao Wu 1,  Peng Lin 1,  Wan Huang 1,  Liangzhi Xie 6,  Zhao-Hui Zheng 7,  Kui Zhang 7,  Jin-Lin Miao 1,  Hong-Yong Cui 1,  Min Huang 1,  Jun Zhang 2,  Ling Fu 2,  Xiang-Min Yang 1,  Zhongpeng Zhao 3,  Shihui Sun 3,  Hongjing Gu 3,  Zhe Wang 8,  Chun-Fu Wang 4,  Yacheng Lu 8,  Ying-Ying Liu 8,  Qing-Yi Wang 8,  Huijie Bian 9,  Ping Zhu 10,  Zhi-Nan Chen 11
Affiliations

Affiliations

  • 1 National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • 2 Beijing Institute of Biotechnology, Beijing, 100071, China.
  • 3 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
  • 4 Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • 5 MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University, Xi'an, 710049, China.
  • 6 Sino Biological Inc., Beijing, 100176, China.
  • 7 Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
  • 8 School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
  • 9 National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China. [email protected].
  • 10 Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. [email protected].
  • 11 National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China. [email protected].
PMID: 33277466 DOI: 10.1038/s41392-020-00426-x
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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