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Structures of Omicron spike complexes and implications for neutralizing antibody development.

Guo H, Gao Y, Li T, Li T, Lu Y, Zheng L, Liu Y, Yang T, Luo F, Song S, Wang W, Yang X, Nguyen HC, Zhang H, Huang A, Jin A, Yang H, Rao Z, Ji X
Cell Rep 39 110770 (2022)
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Cited: 31 times
EuropePMC logo PMID: 35477022

Abstract

The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies.

Articles - 7ws7 mentioned but not cited (2)

  1. Structures of Omicron spike complexes and implications for neutralizing antibody development. Guo H, Gao Y, Li T, Li T, Lu Y, Zheng L, Liu Y, Yang T, Luo F, Song S, Wang W, Yang X, Nguyen HC, Zhang H, Huang A, Jin A, Yang H, Rao Z, Ji X. Cell Rep 39 110770 (2022)
  2. A systematic study on the binding affinity of SARS-CoV-2 spike protein to antibodies. An K, Zhu X, Yan J, Xu P, Hu L, Bai C. AIMS Microbiol 8 595-611 (2022)


Reviews citing this publication (5)

  1. The nervous system during COVID-19: Caught in the crossfire. Natale NR, Lukens JR, Petri WA. Immunol Rev 311 90-111 (2022)
  2. The importance of booster vaccination in the context of Omicron wave. Wei Z, He J, Wang C, Bao J, Leng T, Chen F. Front Immunol 13 977972 (2022)
  3. Distinct Conformations of SARS-CoV-2 Omicron Spike Protein and Its Interaction with ACE2 and Antibody. Lee M, Major M, Hong H. Int J Mol Sci 24 3774 (2023)
  4. Evolution of the SARS-CoV-2 Omicron spike. Parsons RJ, Acharya P. Cell Rep 42 113444 (2023)
  5. Passive antibody therapy in emerging infectious diseases. Yang X. Front Med (2023)

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  4. A comparative study of spike protein of SARS-CoV-2 and its variant Omicron (B.1.1.529) on some immune characteristics. Li X, Li W, Liu Z, Kang Y, Zhang X, Xu Z, Gao Y, Qi Y. Sci Rep 12 17058 (2022)
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  9. Coarse-Grained Molecular Simulations and Ensemble-Based Mutational Profiling of Protein Stability in the Different Functional Forms of the SARS-CoV-2 Spike Trimers: Balancing Stability and Adaptability in BA.1, BA.2 and BA.2.75 Variants. Verkhivker G, Alshahrani M, Gupta G. Int J Mol Sci 24 6642 (2023)
  10. Comparative Analysis of Conformational Dynamics and Systematic Characterization of Cryptic Pockets in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 Spike Complexes with the ACE2 Host Receptor: Confluence of Binding and Structural Plasticity in Mediating Networks of Conserved Allosteric Sites. Alshahrani M, Gupta G, Xiao S, Tao P, Verkhivker G. Viruses 15 2073 (2023)
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  14. Fast principal component analysis for cryo-electron microscopy images. Marshall NF, Mickelin O, Shi Y, Singer A. Biol Imaging 3 e2 (2023)
  15. Inducing enhanced neutralizing antibodies against broad SARS-CoV-2 variants through glycan-shielding multiple non-neutralizing epitopes of RBD. Zhang Q, Yang Y, Lan J, Wang Z, Gao Y, Li X, Mao W, Xie J, Mi LZ, Zhang X, Wang X, Mu X, Mei K. Front Immunol 14 1259386 (2023)
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  17. Optimised Non-Coding Regions of mRNA SARS-CoV-2 Vaccine CV2CoV Improves Homologous and Heterologous Neutralising Antibody Responses. Roth N, Schön J, Hoffmann D, Thran M, Thess A, Mueller SO, Petsch B, Rauch S. Vaccines (Basel) 10 1251 (2022)
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  19. SARS-CoV-2 Omicron Subvariants Balance Host Cell Membrane, Receptor, and Antibody Docking via an Overlapping Target Site. Overduin M, Bhat RK, Kervin TA. Viruses 15 447 (2023)
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  23. Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry. Wang H, Yang Q, Liu X, Xu Z, Shao M, Li D, Duan Y, Tang J, Yu X, Zhang Y, Hao A, Wang Y, Chen J, Zhu C, Guddat L, Chen H, Zhang L, Chen X, Jiang B, Sun L, Rao Z, Yang H. Nat Commun 14 7574 (2023)
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