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Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer.

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Zhan W, Tian X, Zhang X, Xing S, Song W, Liu Q, Hao A, Hu Y, Zhang M, Ying T, Chen Z, Lan F, Sun L
OpenAccess logo J Virol e0048022 (2022)
Related entries: 7wo4, 7wo5, 7wo7, 7woa, 7wob, 7woc, 7wz1, 7wz2

Cited: 14 times
EuropePMC logo PMID: 35924918

Abstract

The continuous emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses new challenges in the fight against the coronavirus disease 2019 (COVID-19) pandemic. The newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over the world. The development of an antibody targeting a conserved and universal epitope is urgently needed. A subset of neutralizing antibodies (NAbs) against COVID-19 from convalescent patients were isolated in our previous study. In this study, we investigated the accommodation of these NAbs to SARS-CoV-2 variants of concern (VOCs), revealing that IgG 553-49 neutralizes pseudovirus of the SARS-CoV-2 Omicron variant. In addition, we determined the cryo-electron microscopy (cryo-EM) structure of the SARS-CoV-2 spike (S) protein complexed with three monoclonal antibodies targeting different epitopes, including 553-49, 553-15, and 553-60. Notably, 553-49 targets a novel conserved epitope and neutralizes the virus by disassembling S trimers. IgG 553-15, an antibody that neutralizes all of the VOCs except Omicron, cross-links two S trimers to form a trimer dimer, demonstrating that 553-15 neutralizes the virus by steric hindrance and virion aggregation. These findings suggest the potential to develop 553-49 and other antibodies targeting this highly conserved epitope as promising therapeutic reagents for COVID-19.

Reviews - 7wog mentioned but not cited (1)

  1. Monoclonal antibody therapies against SARS-CoV-2. Focosi D, McConnell S, Casadevall A, Cappello E, Valdiserra G, Tuccori M. Lancet Infect Dis 22 e311-e326 (2022)

Articles - 7wog mentioned but not cited (1)

  1. Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer. Zhan W, Tian X, Zhang X, Xing S, Song W, Liu Q, Hao A, Hu Y, Zhang M, Ying T, Chen Z, Lan F, Sun L. J Virol 96 e0048022 (2022)


Reviews citing this publication (3)

  1. 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)
  2. Evolution of the SARS-CoV-2 Omicron spike. Parsons RJ, Acharya P. Cell Rep 42 113444 (2023)
  3. Structural understanding of SARS-CoV-2 virus entry to host cells. Le K, Kannappan S, Kim T, Lee JH, Lee HR, Kim KK. Front Mol Biosci 10 1288686 (2023)

Articles citing this publication (9)

  1. A novel monospecific tetravalent IgG1-(scFv)2 version shown enhanced neutralizing and Fc-mediated effector functions against SARS-CoV-2. Gao ZZ, Jiao JY, Zhou YQ, Qi J, Zhu SS, Xu JY, Nie L, Wang HB. 3 Biotech 13 283 (2023)
  2. Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein. Xiang J, Su J, Lan Q, Zhao W, Zhou Y, Xu Y, Niu J, Xia S, Qi Q, Sidhu S, Lu L, Miersch S, Yang B. Commun Biol 5 1179 (2022)
  3. Research Support, Non-U.S. Gov't Cooperative and structural relationships of the trimeric Spike with infectivity and antibody escape of the strains Delta (B.1.617.2) and Omicron (BA.2, BA.5, and BQ.1). de Souza AS, de Souza RF, Guzzo CR. J Comput Aided Mol Des 37 585-606 (2023)
  4. Defining a de novo non-RBM antibody as RBD-8 and its synergistic rescue of immune-evaded antibodies to neutralize Omicron SARS-CoV-2. Rao X, Zhao R, Tong Z, Guo S, Peng W, Liu K, Li S, Wu L, Tong J, Chai Y, Han P, Wang F, Jia P, Li Z, Zhao X, Li D, Zhang R, Zhang X, Zou W, Li W, Wang Q, Gao GF, Wu Y, Dai L, Gao F. Proc Natl Acad Sci U S A 120 e2314193120 (2023)
  5. Letter Defining a highly conserved cryptic epitope for antibody recognition of SARS-CoV-2 variants. Hao A, Song W, Li C, Zhang X, Tu C, Wang X, Wang P, Wu Y, Ying T, Sun L. Signal Transduct Target Ther 8 269 (2023)
  6. Discovery and multimerization of cross-reactive single-domain antibodies against SARS-like viruses to enhance potency and address emerging SARS-CoV-2 variants. Hollingsworth SA, Noland CL, Vroom K, Saha A, Sam M, Gao Q, Zhou H, Grandy DU, Singh S, Wen Z, Warren C, Ma XS, Malashock D, Galli J, Go G, Eddins M, Mayhood T, Sathiyamoorthy K, Fridman A, Raoufi F, Gomez-Llorente Y, Patridge A, Tang Y, Chen SJ, Bailly M, Ji C, Kingsley LJ, Cheng AC, Geierstanger BH, Gorman DM, Zhang L, Pande K. Sci Rep 13 13668 (2023)
  7. Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes. Zhang X, Li Z, Zhang Y, Liu Y, Wang J, Liu B, Chen Q, Wang Q, Fu L, Wang P, Zhong X, Jin L, Yan Q, Chen L, He J, Zhao J, Xiong X. Life Sci Alliance 6 e202201796 (2023)
  8. Recombinant Decoy Exhibits Broad Protection against Omicron and Resistance Potential to Future Variants. Tang H, Ke Y, Wang L, Wu M, Sun T, Zhu J. Pharmaceuticals (Basel) 15 1002 (2022)
  9. Structural basis for broad neutralization of human antibody against Omicron sublineages and evasion by XBB variant. Sun H, Wang Y, Chen X, Jiang Y, Wang S, Huang Y, Liu L, Li Y, Lan M, Guo H, Yuan Q, Zhang Y, Li T, Yu H, Gu Y, Zhang J, Li S, Zheng Z, Zheng Q, Xia N. J Virol 97 e0113723 (2023)


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