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- EMDB-27800: SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific a... -

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Entry
Database: EMDB / ID: EMD-27800
TitleSARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific antibody CoV2-0213
Map data
Sample
  • Complex: SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific antibody CoV2-0213
    • Complex: SARS-CoV-2 Omicron BA.5 Spike trimer
    • Complex: bispecific antibody CoV2-0213
KeywordsSARS-CoV-2 spike / antibody / complex / VIRAL PROTEIN
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 7.7 Å
AuthorsHu Y / Xiong Y
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI) United States
CitationJournal: 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
DepositionAug 7, 2022-
Header (metadata) releaseAug 31, 2022-
Map releaseAug 31, 2022-
UpdateNov 15, 2023-
Current statusNov 15, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_27800.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.07 Å
Density
Contour LevelBy AUTHOR: 0.004
Minimum - Maximum-0.0066466616 - 0.03551491
Average (Standard dev.)-0.0000199489 (±0.001472926)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 410.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_27800_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_27800_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
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Sample components

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Entire : SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific a...

EntireName: SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific antibody CoV2-0213
Components
  • Complex: SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific antibody CoV2-0213
    • Complex: SARS-CoV-2 Omicron BA.5 Spike trimer
    • Complex: bispecific antibody CoV2-0213

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Supramolecule #1: SARS-CoV-2 Omicron BA.5 Spike trimer in complex with bispecific a...

SupramoleculeName: 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

SupramoleculeName: SARS-CoV-2 Omicron BA.5 Spike trimer / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Supramolecule #3: bispecific antibody CoV2-0213

SupramoleculeName: bispecific antibody CoV2-0213 / type: complex / ID: 3 / Parent: 1
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 64.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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

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Image processing

Startup modelType of model: EMDB MAP
EMDB ID:
Final reconstructionResolution.type: BY AUTHOR / Resolution: 7.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 26293
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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