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Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants

Author

Listed:
  • Pengcheng Han

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Emory University
    Southeast University)

  • Chao Su

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    City University of Hong Kong)

  • Yanfang Zhang

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences)

  • Chongzhi Bai

    (Shanxi Academy of Advanced Research and Innovation
    Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine)

  • Anqi Zheng

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Chengpeng Qiao

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences)

  • Qing Wang

    (National Institute of Biological Sciences)

  • Sheng Niu

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Shanxi Agricultural University)

  • Qian Chen

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Anhui University)

  • Yuqin Zhang

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Weiwei Li

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Hanyi Liao

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Jing Li

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences)

  • Zengyuan Zhang

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Heecheol Cho

    (Emory University)

  • Mengsu Yang

    (City University of Hong Kong)

  • Xiaoyu Rong

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Wenzhou Medical University)

  • Yu Hu

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    University of Science and Technology of China)

  • Niu Huang

    (National Institute of Biological Sciences
    Tsinghua University)

  • Jinghua Yan

    (CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences)

  • Qihui Wang

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences)

  • Xin Zhao

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    CAS Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences)

  • George Fu Gao

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    City University of Hong Kong
    University of the Chinese Academy of Sciences)

  • Jianxun Qi

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

Abstract

Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.

Suggested Citation

  • Pengcheng Han & Chao Su & Yanfang Zhang & Chongzhi Bai & Anqi Zheng & Chengpeng Qiao & Qing Wang & Sheng Niu & Qian Chen & Yuqin Zhang & Weiwei Li & Hanyi Liao & Jing Li & Zengyuan Zhang & Heecheol Ch, 2021. "Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26401-w
    DOI: 10.1038/s41467-021-26401-w
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    References listed on IDEAS

    as
    1. Peng Zhou & Xing-Lou Yang & Xian-Guang Wang & Ben Hu & Lei Zhang & Wei Zhang & Hao-Rui Si & Yan Zhu & Bei Li & Chao-Lin Huang & Hui-Dong Chen & Jing Chen & Yun Luo & Hua Guo & Ren-Di Jiang & Mei-Qin L, 2020. "Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin," Nature, Nature, vol. 588(7836), pages 6-6, December.
    2. Jun Lan & Jiwan Ge & Jinfang Yu & Sisi Shan & Huan Zhou & Shilong Fan & Qi Zhang & Xuanling Shi & Qisheng Wang & Linqi Zhang & Xinquan Wang, 2020. "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor," Nature, Nature, vol. 581(7807), pages 215-220, May.
    3. Peng Zhou & Xing-Lou Yang & Xian-Guang Wang & Ben Hu & Lei Zhang & Wei Zhang & Hao-Rui Si & Yan Zhu & Bei Li & Chao-Lin Huang & Hui-Dong Chen & Jing Chen & Yun Luo & Hua Guo & Ren-Di Jiang & Mei-Qin L, 2020. "A pneumonia outbreak associated with a new coronavirus of probable bat origin," Nature, Nature, vol. 579(7798), pages 270-273, March.
    4. Smriti Mallapaty, 2020. "COVID mink analysis shows mutations are not dangerous — yet," Nature, Nature, vol. 587(7834), pages 340-341, November.
    5. Seiya Ozono & Yanzhao Zhang & Hirotaka Ode & Kaori Sano & Toong Seng Tan & Kazuo Imai & Kazuyasu Miyoshi & Satoshi Kishigami & Takamasa Ueno & Yasumasa Iwatani & Tadaki Suzuki & Kenzo Tokunaga, 2021. "SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    6. Sandile Cele & Inbal Gazy & Laurelle Jackson & Shi-Hsia Hwa & Houriiyah Tegally & Gila Lustig & Jennifer Giandhari & Sureshnee Pillay & Eduan Wilkinson & Yeshnee Naidoo & Farina Karim & Yashica Ganga , 2021. "Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma," Nature, Nature, vol. 593(7857), pages 142-146, May.
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    1. Zepeng Xu & Xinrui Kang & Pu Han & Pei Du & Linjie Li & Anqi Zheng & Chuxia Deng & Jianxun Qi & Xin Zhao & Qihui Wang & Kefang Liu & George Fu Gao, 2022. "Binding and structural basis of equine ACE2 to RBDs from SARS-CoV, SARS-CoV-2 and related coronaviruses," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Zhennan Zhao & Jingya Zhou & Mingxiong Tian & Min Huang & Sheng Liu & Yufeng Xie & Pu Han & Chongzhi Bai & Pengcheng Han & Anqi Zheng & Lutang Fu & Yuanzhu Gao & Qi Peng & Ying Li & Yan Chai & Zengyua, 2022. "Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Zhennan Zhao & Yufeng Xie & Bin Bai & Chunliang Luo & Jingya Zhou & Weiwei Li & Yumin Meng & Linjie Li & Dedong Li & Xiaomei Li & Xiaoxiong Li & Xiaoyun Wang & Junqing Sun & Zepeng Xu & Yeping Sun & W, 2023. "Structural basis for receptor binding and broader interspecies receptor recognition of currently circulating Omicron sub-variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Valeria Calvaresi & Antoni G. Wrobel & Joanna Toporowska & Dietmar Hammerschmid & Katie J. Doores & Richard T. Bradshaw & Ricardo B. Parsons & Donald J. Benton & Chloë Roustan & Eamonn Reading & Micha, 2023. "Structural dynamics in the evolution of SARS-CoV-2 spike glycoprotein," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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