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- EMDB-26467: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04 (1 RBD up an... -

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Basic information

Entry
Database: EMDB / ID: EMD-26467
TitleSARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04 (1 RBD up and 1 RDB down)
Map dataSARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04
Sample
  • Complex: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04 (1 RBD up and 1 RDB down)
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / negative staining / Resolution: 26.0 Å
AuthorsTorres JL / Ward AB
Funding support United States, 2 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationOPP1170236 United States
Bill & Melinda Gates FoundationINV-004923 United States
CitationJournal: PLoS Pathog / Year: 2022
Title: A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant.
Authors: Nitin Hingankar / Suprit Deshpande / Payel Das / Zaigham Abbas Rizvi / Constantinos Kurt Wibmer / Poppy Mashilo / Mohammed Yousuf Ansari / Alison Burns / Shawn Barman / Fangzhu Zhao / Sohini ...Authors: Nitin Hingankar / Suprit Deshpande / Payel Das / Zaigham Abbas Rizvi / Constantinos Kurt Wibmer / Poppy Mashilo / Mohammed Yousuf Ansari / Alison Burns / Shawn Barman / Fangzhu Zhao / Sohini Mukherjee / Jonathan L Torres / Souvick Chattopadhyay / Farha Mehdi / Jyoti Sutar / Deepak Kumar Rathore / Kamal Pargai / Janmejay Singh / Sudipta Sonar / Kamini Jakhar / Jyotsna Dandotiya / Sankar Bhattacharyya / Shailendra Mani / Sweety Samal / Savita Singh / Pallavi Kshetrapal / Ramachandran Thiruvengadam / Gaurav Batra / Guruprasad Medigeshi / Andrew B Ward / Shinjini Bhatnagar / Amit Awasthi / Devin Sok / Jayanta Bhattacharya /
Abstract: Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can ...Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of concern (VOCs) that have shown some resistance to vaccine responses. Here we report the isolation of five neutralizing mAbs from an Indian convalescent donor, out of which two (THSC20.HVTR04 and THSC20.HVTR26) showed potent neutralization of SARS-CoV-2 VOCs at picomolar concentrations, including the Delta variant (B.1.617.2). One of these (THSC20.HVTR26) also retained activity against the Omicron variant. These two mAbs target non-overlapping epitopes on the receptor-binding domain (RBD) of the spike protein and prevent virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Furthermore, the mAb cocktail demonstrated protection against the Delta variant at low antibody doses when passively administered in the K18 hACE2 transgenic mice model, highlighting their potential as a cocktail for prophylactic and therapeutic applications. Developing the capacity to rapidly discover and develop mAbs effective against highly transmissible pathogens like coronaviruses at a local level, especially in a low- and middle-income country (LMIC) such as India, will enable prompt responses to future pandemics as an important component of global pandemic preparedness.
History
DepositionMar 21, 2022-
Header (metadata) releaseApr 6, 2022-
Map releaseApr 6, 2022-
UpdateJun 29, 2022-
Current statusJun 29, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_26467.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04
Voxel sizeX=Y=Z: 2.06 Å
Density
Contour LevelBy AUTHOR: 0.0272
Minimum - Maximum-0.03392609 - 0.088389196
Average (Standard dev.)2.5147732e-05 (±0.0036939688)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 527.36 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_26467_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_26467_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04 (1 RBD up an...

EntireName: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04 (1 RBD up and 1 RDB down)
Components
  • Complex: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04 (1 RBD up and 1 RDB down)

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Supramolecule #1: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04 (1 RBD up an...

SupramoleculeName: SARS-CoV-2 6P Mut7 in complex with Fab THSC20.HVTR04 (1 RBD up and 1 RDB down)
type: complex / Chimera: Yes / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
StainingType: NEGATIVE / Material: 2% Uranyl Formate

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Electron microscopy

MicroscopeFEI TECNAI SPIRIT
Electron beamAcceleration voltage: 120 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.5 µm
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Average electron dose: 25.0 e/Å2
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
Final reconstructionResolution.type: BY AUTHOR / Resolution: 26.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 6438

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