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Emerging SARS-CoV-2 Variants of Concern: Spike Protein Mutational Analysis and Epitope for Broad Neutralization
Dhiraj Mannar; James W. Saville; Zehua Sun; Xing Zhu; Michelle M. Marti; Shanti S. Srivastava; Alison M. Berezuk; Steven Zhou; Katharine Tuttle; Michele D. Sobolewski; Andrew Kim; Benjamin R. Treat; Priscila Mayrelle Da Silva Castanha; Jana L. Jacobs; Simon M. Barratt-Boyes; John W. Mellors; Dimitrov S. Dimiter; Wei Li; Sriram Subramaniam.
Affiliation
  • Dhiraj Mannar; The University of British Columbia
  • James W. Saville; The University of British Columbia
  • Zehua Sun; UPMC
  • Xing Zhu; The University of British Columbia
  • Michelle M. Marti; University of Pittsburgh
  • Shanti S. Srivastava; The University of British Columbia
  • Alison M. Berezuk; The University of British Columbia
  • Steven Zhou; The University of British Columbia
  • Katharine Tuttle; The University of British Columbia
  • Michele D. Sobolewski; University of Pittsburgh
  • Andrew Kim; UPMC
  • Benjamin R. Treat; University of Pittsburgh
  • Priscila Mayrelle Da Silva Castanha; University of Pittsburgh
  • Jana L. Jacobs; University of Pittsburgh
  • Simon M. Barratt-Boyes; University of Pittsburgh
  • John W. Mellors; University of Pittsburgh
  • Dimitrov S. Dimiter; UPMC
  • Wei Li; UPMC
  • Sriram Subramaniam; The University of British Columbia
Preprint in English | bioRxiv | ID: ppbiorxiv-473178
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 report the discovery of a novel antibody fragment (VH ab6) that neutralizes all major variants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within 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.
License
cc_by_nc_nd
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
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