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- EMDB-27081: IMM20184 and IMM20253 Fabs in ternary complex with SARS-CoV-2 rec... -

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Basic information

Entry
Database: EMDB / ID: EMD-27081
TitleIMM20184 and IMM20253 Fabs in ternary complex with SARS-CoV-2 receptor binding domain
Map dataIMM20184 and IMM20253 Fabs in complex with SARS-CoV-2 receptor binding domain
Sample
  • Complex: IMM20184 and IMM20253 Fabs in ternary complex with RBD of SARS-CoV-2
    • Complex: IMM20184 Fab
    • Complex: IMM20253 FAb
    • Complex: SARS-CoV-2 RBD
Biological speciesSevere acute respiratory syndrome coronavirus / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.0 Å
AuthorsRobinson MK / Nikitin PN
Funding support United States, 1 items
OrganizationGrant numberCountry
Other private United States
CitationJournal: Sci Immunol / Year: 2022
Title: IMM-BCP-01, a patient-derived anti-SARS-CoV-2 antibody cocktail, is active across variants of concern including Omicron BA.1 and BA.2.
Authors: Pavel A Nikitin / Jillian M DiMuzio / John P Dowling / Nirja B Patel / Jamie L Bingaman-Steele / Baron C Heimbach / Noeleya Henriquez / Chris Nicolescu / Antonio Polley / Eden L Sikorski / ...Authors: Pavel A Nikitin / Jillian M DiMuzio / John P Dowling / Nirja B Patel / Jamie L Bingaman-Steele / Baron C Heimbach / Noeleya Henriquez / Chris Nicolescu / Antonio Polley / Eden L Sikorski / Raymond J Howanski / Mitchell Nath / Halley Shukla / Suzanne M Scheaffer / James P Finn / Li-Fang Liang / Todd Smith / Nadia Storm / Lindsay G A McKay / Rebecca I Johnson / Lauren E Malsick / Anna N Honko / Anthony Griffiths / Michael S Diamond / Purnanand Sarma / Dennis H Geising / Michael J Morin / Matthew K Robinson /
Abstract: Monoclonal antibodies are an efficacious therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, rapid viral mutagenesis led to escape from most of these therapies, ...Monoclonal antibodies are an efficacious therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, rapid viral mutagenesis led to escape from most of these therapies, outlining the need for an antibody cocktail with a broad neutralizing potency. Using an unbiased interrogation of the memory B cell repertoire of patients with convalescent COVID-19, we identified human antibodies with broad antiviral activity in vitro and efficacy in vivo against all tested SARS-CoV-2 variants of concern, including Delta and Omicron BA.1 and BA.2. Here, we describe an antibody cocktail, IMM-BCP-01, that consists of three patient-derived broadly neutralizing antibodies directed at nonoverlapping surfaces on the SARS-CoV-2 Spike protein. Two antibodies, IMM20184 and IMM20190, directly blocked Spike binding to the ACE2 receptor. Binding of the third antibody, IMM20253, to its cryptic epitope on the outer surface of RBD altered the conformation of the Spike Trimer, promoting the release of Spike monomers. These antibodies decreased Omicron SARS-CoV-2 infection in the lungs of Syrian golden hamsters in vivo and potently induced antiviral effector response in vitro, including phagocytosis, ADCC, and complement pathway activation. Our preclinical data demonstrated that the three-antibody cocktail IMM-BCP-01 could be a promising means for preventing or treating infection of SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2, in susceptible individuals.
History
DepositionMay 24, 2022-
Header (metadata) releaseJun 8, 2022-
Map releaseJun 8, 2022-
UpdateSep 21, 2022-
Current statusSep 21, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_27081.png

Downloads & links

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Map

FileDownload / File: emd_27081.map.gz / Format: CCP4 / Size: 166.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationIMM20184 and IMM20253 Fabs in complex with SARS-CoV-2 receptor binding domain
Voxel sizeX=Y=Z: 0.923 Å
Density
Contour LevelBy AUTHOR: 0.66
Minimum - Maximum-4.8360085 - 5.680439
Average (Standard dev.)-0.000471981 (±0.06653402)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions352352352
Spacing352352352
CellA=B=C: 324.896 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_27081_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_27081_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : IMM20184 and IMM20253 Fabs in ternary complex with RBD of SARS-CoV-2

EntireName: IMM20184 and IMM20253 Fabs in ternary complex with RBD of SARS-CoV-2
Components
  • Complex: IMM20184 and IMM20253 Fabs in ternary complex with RBD of SARS-CoV-2
    • Complex: IMM20184 Fab
    • Complex: IMM20253 FAb
    • Complex: SARS-CoV-2 RBD

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Supramolecule #1: IMM20184 and IMM20253 Fabs in ternary complex with RBD of SARS-CoV-2

SupramoleculeName: IMM20184 and IMM20253 Fabs in ternary complex with RBD of SARS-CoV-2
type: complex / Chimera: Yes / ID: 1 / Parent: 0
Source (natural)Organism: Severe acute respiratory syndrome coronavirus

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Supramolecule #2: IMM20184 Fab

SupramoleculeName: IMM20184 Fab / type: complex / Chimera: Yes / ID: 2 / Parent: 1
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Mammalia (mammals)

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Supramolecule #3: IMM20253 FAb

SupramoleculeName: IMM20253 FAb / type: complex / Chimera: Yes / ID: 3 / Parent: 1
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Mammalia (mammals)

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Supramolecule #4: SARS-CoV-2 RBD

SupramoleculeName: SARS-CoV-2 RBD / type: complex / Chimera: Yes / ID: 4 / Parent: 1
Source (natural)Organism: Severe acute respiratory syndrome coronavirus
Recombinant expressionOrganism: Mammalia (mammals)

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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

MicroscopeTFS GLACIOS
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 19.59 e/Å2

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

1m71


Details: 1M71 for Fabs and 7JVB for RBD
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 300000
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementProtocol: RIGID BODY FIT

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