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SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Ke Wang, Wei Chen, Yu-Sen Zhou, Jian-Qi Lian, Zheng Zhang, Peng Du, Li Gong, Yang Zhang, Hong-Yong Cui, Jie-Jie Geng, Bin Wang, Xiu-Xuan Sun, Chun-Fu Wang, Xu Yang, Peng Lin, Yong-Qiang Deng, Ding Wei, Xiang-Min Yang, Yu-Meng Zhu, Kui Zhang, Zhao-Hui Zheng, Jin-Lin Miao, Ting Guo, Ying Shi, Jun Zhang, Ling Fu, Qing-Yi Wang, Huijie Bian, Ping Zhu, Zhi-Nan Chen
doi: https://doi.org/10.1101/2020.03.14.988345
Ke Wang
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Wei Chen
4Beijing Institute of Biotechnology, Beijing, China, 100071
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Yu-Sen Zhou
4Beijing Institute of Biotechnology, Beijing, China, 100071
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Jian-Qi Lian
3Tangdu Hospital, Fourth Military Medical University, Xi’an, China, 710038
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Zheng Zhang
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Peng Du
4Beijing Institute of Biotechnology, Beijing, China, 100071
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Li Gong
3Tangdu Hospital, Fourth Military Medical University, Xi’an, China, 710038
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Yang Zhang
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Hong-Yong Cui
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Jie-Jie Geng
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Bin Wang
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Xiu-Xuan Sun
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Chun-Fu Wang
3Tangdu Hospital, Fourth Military Medical University, Xi’an, China, 710038
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Xu Yang
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Peng Lin
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Yong-Qiang Deng
4Beijing Institute of Biotechnology, Beijing, China, 100071
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Ding Wei
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Xiang-Min Yang
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Yu-Meng Zhu
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Kui Zhang
2Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an, China, 710032
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Zhao-Hui Zheng
2Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an, China, 710032
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Jin-Lin Miao
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Ting Guo
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Ying Shi
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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Jun Zhang
4Beijing Institute of Biotechnology, Beijing, China, 100071
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Ling Fu
4Beijing Institute of Biotechnology, Beijing, China, 100071
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Qing-Yi Wang
5Department of Foreign Languages, Fourth Military Medical University, Xi’an, China, 710032
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Huijie Bian
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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  • For correspondence: znchen@fmmu.edu.cn zhuping@fmmu.edu.cn hjbian@fmmu.edu.cn
Ping Zhu
2Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an, China, 710032
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  • For correspondence: znchen@fmmu.edu.cn zhuping@fmmu.edu.cn hjbian@fmmu.edu.cn
Zhi-Nan Chen
1National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China, 710032
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  • For correspondence: znchen@fmmu.edu.cn zhuping@fmmu.edu.cn hjbian@fmmu.edu.cn
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SUMMARY

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 μg/mL and IC50 of 15.16 μg/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85×10−7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

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Posted March 14, 2020.
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SARS-CoV-2 invades host cells via a novel route: CD147-spike protein
Ke Wang, Wei Chen, Yu-Sen Zhou, Jian-Qi Lian, Zheng Zhang, Peng Du, Li Gong, Yang Zhang, Hong-Yong Cui, Jie-Jie Geng, Bin Wang, Xiu-Xuan Sun, Chun-Fu Wang, Xu Yang, Peng Lin, Yong-Qiang Deng, Ding Wei, Xiang-Min Yang, Yu-Meng Zhu, Kui Zhang, Zhao-Hui Zheng, Jin-Lin Miao, Ting Guo, Ying Shi, Jun Zhang, Ling Fu, Qing-Yi Wang, Huijie Bian, Ping Zhu, Zhi-Nan Chen
bioRxiv 2020.03.14.988345; doi: https://doi.org/10.1101/2020.03.14.988345
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SARS-CoV-2 invades host cells via a novel route: CD147-spike protein
Ke Wang, Wei Chen, Yu-Sen Zhou, Jian-Qi Lian, Zheng Zhang, Peng Du, Li Gong, Yang Zhang, Hong-Yong Cui, Jie-Jie Geng, Bin Wang, Xiu-Xuan Sun, Chun-Fu Wang, Xu Yang, Peng Lin, Yong-Qiang Deng, Ding Wei, Xiang-Min Yang, Yu-Meng Zhu, Kui Zhang, Zhao-Hui Zheng, Jin-Lin Miao, Ting Guo, Ying Shi, Jun Zhang, Ling Fu, Qing-Yi Wang, Huijie Bian, Ping Zhu, Zhi-Nan Chen
bioRxiv 2020.03.14.988345; doi: https://doi.org/10.1101/2020.03.14.988345

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