7WOB
SARS-CoV-2 Spike in complex with IgG 553-60 (2-up trimer)
Summary for 7WOB
| Entry DOI | 10.2210/pdb7wob/pdb |
| EMDB information | 32647 |
| Descriptor | Spike glycoprotein, mAb60 VH, mAb60 VL, ... (4 entities in total) |
| Functional Keywords | sars-cov-2, spike, antibody, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 9 |
| Total formula weight | 578662.90 |
| Authors | Zhan, W.Q.,Zhang, X.,Chen, Z.G.,Sun, L. (deposition date: 2022-01-21, release date: 2022-07-20, Last modification date: 2024-11-13) |
| Primary citation | 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. Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer. J.Virol., 96:e0048022-e0048022, 2022 Cited by PubMed 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. The emergence of the Omicron strain of SARS-CoV-2 caused higher immune escape, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. In this study, we identified a SARS-CoV-2 neutralizing antibody, 553-49, which neutralizes all variants by targeting a completely conserved novel epitope. In addition, we revealed that IgG 553-15 neutralizes SARS-CoV-2 by cross-linking virions and that 553-60 functions by blocking receptor binding. Comparison of different receptor binding domain (RBD) epitopes revealed that the 553-49 epitope is hidden in the S trimer and keeps a high degree of conservation during SARS-CoV-2 evolution, making 553-49 a promising therapeutic reagent against the emerging Omicron and future variants of SARS-CoV-2. PubMed: 35924918DOI: 10.1128/jvi.00480-22 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.25 Å) |
Structure validation
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