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- EMDB-25618: SARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments -

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Basic information

Entry
Database: EMDB / ID: EMD-25618
TitleSARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments
Map dataSARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments
Sample
  • Complex: SARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments
KeywordsSARS-CoV-2 / spike / VFLIP / Ab12 / VIRAL PROTEIN
Biological speciesCell-free gateway cloning vector C-term 8xHis pCellFree_G02 (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.6 Å
AuthorsOlmedillas E / Ollmann-Saphire E
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Nat Commun / Year: 2022
Title: IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern.
Authors: Matthew R Chang / Luke Tomasovic / Natalia A Kuzmina / Adam J Ronk / Patrick O Byrne / Rebecca Johnson / Nadia Storm / Eduardo Olmedillas / Yixuan J Hou / Alexandra Schäfer / Sarah R Leist ...Authors: Matthew R Chang / Luke Tomasovic / Natalia A Kuzmina / Adam J Ronk / Patrick O Byrne / Rebecca Johnson / Nadia Storm / Eduardo Olmedillas / Yixuan J Hou / Alexandra Schäfer / Sarah R Leist / Longping V Tse / Hanzhong Ke / Christian Coherd / Katrina Nguyen / Maliwan Kamkaew / Anna Honko / Quan Zhu / Galit Alter / Erica Ollmann Saphire / Jason S McLellan / Anthony Griffiths / Ralph S Baric / Alexander Bukreyev / Wayne A Marasco /
Abstract: Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being ...Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern.
History
DepositionDec 5, 2021-
Header (metadata) releaseSep 7, 2022-
Map releaseSep 7, 2022-
UpdateJan 17, 2024-
Current statusJan 17, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_25618.png

Downloads & links

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Map

FileDownload / File: emd_25618.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.66 Å/pix.
x 256 pix.
= 168.96 Å		0.66 Å/pix.
x 256 pix.
= 168.96 Å		0.66 Å/pix.
x 256 pix.
= 168.96 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.66 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.133
Minimum - Maximum-0.32274494 - 0.8282887
Average (Standard dev.)-0.00026058228 (±0.03434518)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 168.96 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : SARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments

EntireName: SARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments
Components
  • Complex: SARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments

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Supramolecule #1: SARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments

SupramoleculeName: SARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Cell-free gateway cloning vector C-term 8xHis pCellFree_G02 (others)

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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

Concentration1.5 mg/mL
BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON I (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 150352
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

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