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SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization

Author

Listed:
  • Dhiraj Mannar

    (University of British Columbia)

  • James W. Saville

    (University of British Columbia)

  • Zehua Sun

    (University of Pittsburgh School of Medicine)

  • Xing Zhu

    (University of British Columbia)

  • Michelle M. Marti

    (University of Pittsburgh)

  • Shanti S. Srivastava

    (University of British Columbia)

  • Alison M. Berezuk

    (University of British Columbia)

  • Steven Zhou

    (University of British Columbia)

  • Katharine S. Tuttle

    (University of British Columbia)

  • Michele D. Sobolewski

    (University of Pittsburgh School of Medicine)

  • Andrew Kim

    (University of Pittsburgh School of Medicine)

  • Benjamin R. Treat

    (University of Pittsburgh)

  • Priscila Mayrelle Silva Castanha

    (University of Pittsburgh)

  • Jana L. Jacobs

    (University of Pittsburgh School of Medicine)

  • Simon M. Barratt-Boyes

    (University of Pittsburgh)

  • John W. Mellors

    (University of Pittsburgh School of Medicine)

  • Dimiter S. Dimitrov

    (University of Pittsburgh School of Medicine)

  • Wei Li

    (University of Pittsburgh School of Medicine)

  • Sriram Subramaniam

    (University of British Columbia
    Gandeeva Therapeutics Inc.)

Abstract

Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (VH ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants.

Suggested Citation

  • Dhiraj Mannar & James W. Saville & Zehua Sun & Xing Zhu & Michelle M. Marti & Shanti S. Srivastava & Alison M. Berezuk & Steven Zhou & Katharine S. Tuttle & Michele D. Sobolewski & Andrew Kim & Benjam, 2022. "SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32262-8
    DOI: 10.1038/s41467-022-32262-8
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    2. Hu Li & Huarui Gong & Tsz Hung Wong & Jingkun Zhou & Yuqiong Wang & Long Lin & Ying Dou & Huiling Jia & Xingcan Huang & Zhan Gao & Rui Shi & Ya Huang & Zhenlin Chen & Wooyoung PARK & Ji Yu Li & Hongwe, 2023. "Wireless, battery-free, multifunctional integrated bioelectronics for respiratory pathogens monitoring and severity evaluation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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