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Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV

Author

Listed:
  • Xiuyuan Ou

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yan Liu

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xiaobo Lei

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Pei Li

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Dan Mi

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lili Ren

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Li Guo

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Ruixuan Guo

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Ting Chen

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jiaxin Hu

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zichun Xiang

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zhixia Mu

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xing Chen

    (Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC))

  • Jieyong Chen

    (Hengshui Third People’s Hospital)

  • Keping Hu

    (Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC))

  • Qi Jin

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jianwei Wang

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zhaohui Qian

    (Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.

Suggested Citation

  • Xiuyuan Ou & Yan Liu & Xiaobo Lei & Pei Li & Dan Mi & Lili Ren & Li Guo & Ruixuan Guo & Ting Chen & Jiaxin Hu & Zichun Xiang & Zhixia Mu & Xing Chen & Jieyong Chen & Keping Hu & Qi Jin & Jianwei Wang , 2020. "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15562-9
    DOI: 10.1038/s41467-020-15562-9
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    Cited by:

    1. Milad Haghani & Pegah Varamini, 2021. "Temporal evolution, most influential studies and sleeping beauties of the coronavirus literature," Scientometrics, Springer;Akadémiai Kiadó, vol. 126(8), pages 7005-7050, August.
    2. Qi Zhang & Weichun Tang & Eduardo Stancanelli & Eunkyung Jung & Zulfeqhar Syed & Vijayakanth Pagadala & Layla Saidi & Catherine Z. Chen & Peng Gao & Miao Xu & Ivan Pavlinov & Bing Li & Wenwei Huang & , 2023. "Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Leire Campos-Mata & Benjamin Trinité & Andrea Modrego & Sonia Tejedor Vaquero & Edwards Pradenas & Anna Pons-Grífols & Natalia Rodrigo Melero & Diego Carlero & Silvia Marfil & César Santiago & Dàlia R, 2024. "A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. James Brett Case & Samantha Mackin & John M. Errico & Zhenlu Chong & Emily A. Madden & Bradley Whitener & Barbara Guarino & Michael A. Schmid & Kim Rosenthal & Kuishu Ren & Ha V. Dang & Gyorgy Snell &, 2022. "Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Tingting Li & Xiaojian Han & Chenjian Gu & Hangtian Guo & Huajun Zhang & Yingming Wang & Chao Hu & Kai Wang & Fengjiang Liu & Feiyang Luo & Yanan Zhang & Jie Hu & Wang Wang & Shenglong Li & Yanan Hao , 2021. "Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    6. Fabian Zech & Daniel Schniertshauer & Christoph Jung & Alexandra Herrmann & Arne Cordsmeier & Qinya Xie & Rayhane Nchioua & Caterina Prelli Bozzo & Meta Volcic & Lennart Koepke & Janis A. Müller & Jan, 2021. "Spike residue 403 affects binding of coronavirus spikes to human ACE2," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    7. Uddhav Timilsina & Supawadee Umthong & Emily B. Ivey & Brandon Waxman & Spyridon Stavrou, 2022. "SARS-CoV-2 ORF7a potently inhibits the antiviral effect of the host factor SERINC5," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Hengrui Liu & Sho Iketani & Arie Zask & Nisha Khanizeman & Eva Bednarova & Farhad Forouhar & Brandon Fowler & Seo Jung Hong & Hiroshi Mohri & Manoj S. Nair & Yaoxing Huang & Nicholas E. S. Tay & Sumin, 2022. "Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    9. Naoko Iwata-Yoshikawa & Masatoshi Kakizaki & Nozomi Shiwa-Sudo & Takashi Okura & Maino Tahara & Shuetsu Fukushi & Ken Maeda & Miyuki Kawase & Hideki Asanuma & Yuriko Tomita & Ikuyo Takayama & Shutoku , 2022. "Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    10. Wenjuan Dong & Jing Wang & Lei Tian & Jianying Zhang & Erik W. Settles & Chao Qin & Daniel R. Steinken-Kollath & Ashley N. Itogawa & Kimberly R. Celona & Jinhee Yi & Mitchell Bryant & Heather Mead & S, 2023. "Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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