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Yorodumi- EMDB-27800: SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific a... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27800 | |||||||||
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Title | SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific antibody CoV2-0213 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | SARS-CoV-2 spike / antibody / complex / VIRAL PROTEIN | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.7 Å | |||||||||
Authors | Hu Y / Xiong Y | |||||||||
Funding support | United States, 1 items
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Citation | Journal: bioRxiv / Year: 2023 Title: Function and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages. Authors: Ping Ren / Yingxia Hu / Lei Peng / Luojia Yang / Kazushi Suzuki / Zhenhao Fang / Meizhu Bai / Liqun Zhou / Yanzhi Feng / Yongji Zou / Yong Xiong / Sidi Chen / Abstract: The SARS-CoV-2 variant, Omicron (B.1.1.529), rapidly swept the world since its emergence. Compared with previous variants, Omicron has a high number of mutations, especially those in its spike ...The SARS-CoV-2 variant, Omicron (B.1.1.529), rapidly swept the world since its emergence. Compared with previous variants, Omicron has a high number of mutations, especially those in its spike glycoprotein that drastically dampen or abolish the efficacy of currently available vaccines and therapeutic antibodies. Several major sublineages of Omicron evolved, including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, BA.4/5, and BA.2.75, which rapidly changing the global and regional landscape of the pandemic. Although vaccines are available, therapeutic antibodies remain critical for infected and especially hospitalized patients. To address this, we have designed and generated a panel of human/humanized therapeutic bispecific antibodies against Omicron and its sub-lineage variants, with activity spectrum against other lineages. Among these, the top clone CoV2-0213 has broadly potent activities against multiple SARS-CoV-2 ancestral and Omicron lineages, including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, BA.4/5, and BA.2.75. We have solved the cryo-EM structure of the lead bi-specific antibody CoV-0213 and its major Fab arm MB.02. Three-dimensional structural analysis shows distinct epitope of antibody - spike receptor binding domain (RBD) interactions and reveals that both Fab fragments of CoV2-0213 can simultaneously target one single spike RBD or two adjacent ones in the same spike trimer, further corroborating its mechanism of action. CoV2-0213 represents a unique and potent broad-spectrum SARS-CoV-2 neutralizing bispecific antibody (nbsAb) against the currently circulating major Omicron variants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.3, and BA.4/5). CoV2-0213 is primarily human and ready for translational testing as a countermeasure against the ever-evolving pathogen. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27800.map.gz | 171.3 MB | EMDB map data format | |
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Header (meta data) | emd-27800-v30.xml emd-27800.xml | 14.2 KB 14.2 KB | Display Display | EMDB header |
Images | emd_27800.png | 39.9 KB | ||
Filedesc metadata | emd-27800.cif.gz | 3.9 KB | ||
Others | emd_27800_half_map_1.map.gz emd_27800_half_map_2.map.gz | 172.1 MB 172.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27800 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27800 | HTTPS FTP |
-Validation report
Summary document | emd_27800_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
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Full document | emd_27800_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_27800_validation.xml.gz | 15.5 KB | Display | |
Data in CIF | emd_27800_validation.cif.gz | 18.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27800 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27800 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_27800.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_27800_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_27800_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific a...
Entire | Name: SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific antibody CoV2-0213 |
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Components |
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-Supramolecule #1: SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific a...
Supramolecule | Name: SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific antibody CoV2-0213 type: complex / ID: 1 / Parent: 0 |
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-Supramolecule #2: SARS-CoV-2 Omicron BA.5 Spike trimer
Supramolecule | Name: SARS-CoV-2 Omicron BA.5 Spike trimer / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: bispecific antibody CoV2-0213
Supramolecule | Name: bispecific antibody CoV2-0213 / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 7.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 26293 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |