Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
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Journal
IF	>30 >20 >10 >5 all

Title	Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer.
Journal, issue, pages	J Virol, Vol. 96, Issue 16, Page e0048022, Year 2022
Publish date	Aug 24, 2022
Authors	Wuqiang Zhan / Xiaolong Tian / Xiang Zhang / Shenghui Xing / Wenping Song / Qianying Liu / Aihua Hao / Yuxia Hu / Meng Zhang / Tianlei Ying / Zhenguo Chen / Fei Lan / Lei Sun /
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 ...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.
External links	J Virol / PubMed:35924918 / PubMed Central
Methods	EM (single particle)
Resolution	2.7 - 4.47 Å
Structure data	32638 7wo4 EMDB-32638, PDB-7wo4: SARS-CoV-2 Spike in complex with IgG 553-15 (S-553-15 dimer trimer ) Method: EM (single particle) / Resolution: 4.47 Å 32639 7wo5 EMDB-32639, PDB-7wo5: SARS-CoV-2 Spike in complex with IgG 553-15 (S-553-15 trimer) Method: EM (single particle) / Resolution: 3.45 Å 32641 7wo7 EMDB-32641, PDB-7wo7: Locally refined region of SARS-CoV-2 Spike in complex with IgG 553-15 Method: EM (single particle) / Resolution: 3.8 Å 32646 7woa EMDB-32646, PDB-7woa: SARS-CoV-2 Spike in complex with IgG 553-60 (1-up trimer) Method: EM (single particle) / Resolution: 3.25 Å 32647 7wob EMDB-32647, PDB-7wob: SARS-CoV-2 Spike in complex with IgG 553-60 (2-up trimer) Method: EM (single particle) / Resolution: 3.25 Å 32648 7woc EMDB-32648, PDB-7woc: Locally refined region of SARS-CoV-2 Spike in complex with IgG 553-60 Method: EM (single particle) / Resolution: 3.35 Å 32651 7wog EMDB-32651, PDB-7wog: SARS-CoV-2 Omicron S monomer complexed with 553-49 Method: EM (single particle) / Resolution: 4.06 Å 32901 7wz1 EMDB-32901, PDB-7wz1: SARS-CoV-2 Omicron Spike trimer Method: EM (single particle) / Resolution: 3.4 Å 32902 7wz2 EMDB-32902, PDB-7wz2: SARS-CoV-2 (D614G) Spike trimer Method: EM (single particle) / Resolution: 2.7 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine
Source	severe acute respiratory syndrome coronavirus 2 homo sapiens (human)
Keywords	VIRAL PROTEIN / SARS-COV-2 / Spike / Antibody / Omicron