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The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS

Tong Meng, Hao Cao, Hao Zhang, Zijian Kang, Da Xu, Haiyi Gong, Jing Wang, Zifu Li, Xingang Cui, Huji Xu, Haifeng Wei, Xiuwu Pan, Rongrong Zhu, Jianru Xiao, Wang Zhou, Liming Cheng, Jianmin Liu
doi: https://doi.org/10.1101/2020.02.08.926006
Tong Meng
1Division of Spine, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, 200065 Shanghai, China
2Tongji University Cancer Center, School of Medicine, Tongji University, 200092 Shanghai, China
10Qiu-Jiang Bioinformatics Institute, 200003 Shanghai, China
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Hao Cao
3School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, China
4Peking-Tsinghua Center for Life Sciences, TsinghuaUniversity, 100084 Beijing, China
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Hao Zhang
5Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China
10Qiu-Jiang Bioinformatics Institute, 200003 Shanghai, China
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Zijian Kang
6Department of Rheumatology and Immunology, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China
10Qiu-Jiang Bioinformatics Institute, 200003 Shanghai, China
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Da Xu
7Depanrtment of Urology, The Third Affiliated Hospital of Second Military Medical University, 201805 Shanghai, China
10Qiu-Jiang Bioinformatics Institute, 200003 Shanghai, China
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Haiyi Gong
5Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China
10Qiu-Jiang Bioinformatics Institute, 200003 Shanghai, China
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Jing Wang
8Department of Neurosurgery, Changhai hospital, Second Military Medical University, 200003 Shanghai, China
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Zifu Li
8Department of Neurosurgery, Changhai hospital, Second Military Medical University, 200003 Shanghai, China
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Xingang Cui
7Depanrtment of Urology, The Third Affiliated Hospital of Second Military Medical University, 201805 Shanghai, China
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Huji Xu
4Peking-Tsinghua Center for Life Sciences, TsinghuaUniversity, 100084 Beijing, China
6Department of Rheumatology and Immunology, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China
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Haifeng Wei
5Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China
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Xiuwu Pan
7Depanrtment of Urology, The Third Affiliated Hospital of Second Military Medical University, 201805 Shanghai, China
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Rongrong Zhu
9Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Science and Technology, Tongji University, 200092 Shanghai, China
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Jianru Xiao
5Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China
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Wang Zhou
4Peking-Tsinghua Center for Life Sciences, TsinghuaUniversity, 100084 Beijing, China
10Qiu-Jiang Bioinformatics Institute, 200003 Shanghai, China
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Liming Cheng
1Division of Spine, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, 200065 Shanghai, China
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Jianmin Liu
8Department of Neurosurgery, Changhai hospital, Second Military Medical University, 200003 Shanghai, China
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  • For correspondence: chstroke@163.com
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Abstract

At the end of 2019, the SARS-CoV-2 induces an ongoing outbreak of pneumonia in China1, even more spread than SARS-CoV infection2. The entry of SARS-CoV into host cells mainly depends on the cell receptor (ACE2) recognition and spike protein cleavage-induced cell membrane fusion3,4. The spike protein of SARS-CoV-2 also binds to ACE2 with a similar affinity, whereas its spike protein cleavage remains unclear5,6. Here we show that an insertion sequence in the spike protein of SARS-CoV-2 enhances the cleavage efficiency, and besides pulmonary alveoli, intestinal and esophagus epithelium were also the target tissues of SARS-CoV-2. Compared with SARS-CoV, we found a SPRR insertion in the S1/S2 protease cleavage sites of SARS-CoV-2 spike protein increasing the cleavage efficiency by the protein sequence aligment and furin score calculation. Additionally, the insertion sequence facilitates the formation of an extended loop which was more suitable for protease recognition by the homology modeling and molicular docking. Furthermore, the single-cell transcriptomes identified that ACE2 and TMPRSSs are highly coexpressed in AT2 cells of lung, along with esophageal upper epithelial cells and absorptive enterocytes. Our results provide the bioinformatics evidence for the increased spike protein cleavage of SARS-CoV-2 and indicate its potential target cells.

Footnotes

  • ↵* e-mail: chstroke{at}163.com; limingcheng{at}tongji.edu.cn; brilliant212{at}163.com; jianruxiao83{at}163.com

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 16, 2020.
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The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS
Tong Meng, Hao Cao, Hao Zhang, Zijian Kang, Da Xu, Haiyi Gong, Jing Wang, Zifu Li, Xingang Cui, Huji Xu, Haifeng Wei, Xiuwu Pan, Rongrong Zhu, Jianru Xiao, Wang Zhou, Liming Cheng, Jianmin Liu
bioRxiv 2020.02.08.926006; doi: https://doi.org/10.1101/2020.02.08.926006
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The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS
Tong Meng, Hao Cao, Hao Zhang, Zijian Kang, Da Xu, Haiyi Gong, Jing Wang, Zifu Li, Xingang Cui, Huji Xu, Haifeng Wei, Xiuwu Pan, Rongrong Zhu, Jianru Xiao, Wang Zhou, Liming Cheng, Jianmin Liu
bioRxiv 2020.02.08.926006; doi: https://doi.org/10.1101/2020.02.08.926006

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