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- EMDB-46892: Structure of SARS-CoV-2 spike in complex with antibody Fab COVIC-154 -

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Entry
Database: EMDB / ID: EMD-46892
TitleStructure of SARS-CoV-2 spike in complex with antibody Fab COVIC-154
Map data
Sample
  • Complex: Structure of SARS-CoV-2 spike in complex with antibody COVIC-154 Fab
    • Complex: Antibody COVIC-154 Fab Heavy Chain,Antibody COVIC-154 Fab Light Chain
      • Protein or peptide: Antibody Fab COVIC-154 Heavy Chain
      • Protein or peptide: Antibody Fab COVIC-154 Light Chain
    • Complex: SARS-CoV-2 Spike Glycoprotein
      • Protein or peptide: Spike glycoprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsVIRAL PROTEIN / glycoprotein / immune system / antibody / SARS-CoV-2 / COVID / VIRAL PROTEIN-Immune System complex / coronavirus / ANTIVIRAL PROTEIN
Function / homology
Function and homology information


Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / membrane fusion / Attachment and Entry / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / receptor ligand activity / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane
Similarity search - Function
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2
Similarity search - Domain/homology
Biological speciesHomo sapiens (human) / Severe acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 2.7 Å
AuthorsYu X / Saphire EO
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)U19 AI142790-03S1 United States
Bill & Melinda Gates FoundationINV-0006133 United States
GHR Foundation United States
CitationJournal: Cell Rep / Year: 2025
Title: A global collaboration for systematic analysis of broad-ranging antibodies against the SARS-CoV-2 spike protein.
Authors: Sharon L Schendel / Xiaoying Yu / Peter J Halfmann / Jarjapu Mahita / Brendan Ha / Kathryn M Hastie / Haoyang Li / Daniel Bedinger / Camille Troup / Kan Li / Natalia Kuzmina / Jordi B ...Authors: Sharon L Schendel / Xiaoying Yu / Peter J Halfmann / Jarjapu Mahita / Brendan Ha / Kathryn M Hastie / Haoyang Li / Daniel Bedinger / Camille Troup / Kan Li / Natalia Kuzmina / Jordi B Torrelles / Jennifer E Munt / Melissa Maddocks / Mary Osei-Twum / Heather M Callaway / / Stephen Reece / Anne Palser / Paul Kellam / S Moses Dennison / Richard H C Huntwork / Gillian Q Horn / Milite Abraha / Elizabeth Feeney / Luis Martinez-Sobrido / Paula A Pino / Amberlee Hicks / Chengjin Ye / Jun-Gyu Park / Billie Maingot / Sivakumar Periasamy / Michael Mallory / Trevor Scobey / Marie-Noelle Lepage / Natalie St-Amant / Sarwat Khan / Anaïs Gambiez / / Ralph S Baric / Alexander Bukreyev / Luc Gagnon / Timothy Germann / Yoshihiro Kawaoka / Georgia D Tomaras / Bjoern Peters / Erica Ollmann Saphire /
Abstract: The Coronavirus Immunotherapeutic Consortium (CoVIC) conducted side-by-side comparisons of over 400 anti-SARS-CoV-2 spike therapeutic antibody candidates contributed by large and small companies as ...The Coronavirus Immunotherapeutic Consortium (CoVIC) conducted side-by-side comparisons of over 400 anti-SARS-CoV-2 spike therapeutic antibody candidates contributed by large and small companies as well as academic groups on multiple continents. Nine reference labs analyzed antibody features, including in vivo protection in a mouse model of infection, spike protein affinity, high-resolution epitope binning, ACE-2 binding blockage, structures, and neutralization of pseudovirus and authentic virus infection, to build a publicly accessible dataset in the database CoVIC-DB. High-throughput, high-resolution binning of CoVIC antibodies defines a broad and predictive landscape of antibody epitopes on the SARS-CoV-2 spike protein and identifies features associated with durable potency against multiple SARS-CoV-2 variants of concern and high in vivo efficacy. Results of the CoVIC studies provide a guide for selecting effective and durable antibody therapeutics and for immunogen design as well as providing a framework for rapid response to future viral disease outbreaks.
History
DepositionSep 4, 2024-
Header (metadata) releaseApr 16, 2025-
Map releaseApr 16, 2025-
UpdateApr 16, 2025-
Current statusApr 16, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46892.png

Downloads & links

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Map

FileDownload / File: emd_46892.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.99 Å/pix.
x 400 pix.
= 396. Å		0.99 Å/pix.
x 400 pix.
= 396. Å		0.99 Å/pix.
x 400 pix.
= 396. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.99 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.09
Minimum - Maximum-0.28191733 - 0.67064446
Average (Standard dev.)0.00004714462 (±0.014126166)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 396.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_46892_half_map_1.map
Projections & Slices
AxesZYX

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Density Histograms

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Half map: #1

Fileemd_46892_half_map_2.map
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Sample components

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Entire : Structure of SARS-CoV-2 spike in complex with antibody COVIC-154 Fab

EntireName: Structure of SARS-CoV-2 spike in complex with antibody COVIC-154 Fab
Components
  • Complex: Structure of SARS-CoV-2 spike in complex with antibody COVIC-154 Fab
    • Complex: Antibody COVIC-154 Fab Heavy Chain,Antibody COVIC-154 Fab Light Chain
      • Protein or peptide: Antibody Fab COVIC-154 Heavy Chain
      • Protein or peptide: Antibody Fab COVIC-154 Light Chain
    • Complex: SARS-CoV-2 Spike Glycoprotein
      • Protein or peptide: Spike glycoprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Structure of SARS-CoV-2 spike in complex with antibody COVIC-154 Fab

SupramoleculeName: Structure of SARS-CoV-2 spike in complex with antibody COVIC-154 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3

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Supramolecule #2: Antibody COVIC-154 Fab Heavy Chain,Antibody COVIC-154 Fab Light Chain

SupramoleculeName: Antibody COVIC-154 Fab Heavy Chain,Antibody COVIC-154 Fab Light Chain
type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: SARS-CoV-2 Spike Glycoprotein

SupramoleculeName: SARS-CoV-2 Spike Glycoprotein / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Macromolecule #1: Antibody Fab COVIC-154 Heavy Chain

MacromoleculeName: Antibody Fab COVIC-154 Heavy Chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.371874 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQT PGKGLEWVSG ISWNSGSIGY ADSVKGRFTI SRDNAKNSLY LQMNSLRAE DTALYYCTKD LGLGIGFYYG LDVWGQGTTV TVSS

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Macromolecule #2: Antibody Fab COVIC-154 Light Chain

MacromoleculeName: Antibody Fab COVIC-154 Light Chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.703101 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
AIQMTQSPSS LSTSVGDRVT ITCRASQGIR NDLGWYQLKP GKAPKLLIYD ASTLQSGVPS RFSGSGSGTD FTLTISSLEP EDLATYYCL HHYTYPWTFG HGTKVELK

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Macromolecule #3: Spike glycoprotein

MacromoleculeName: Spike glycoprotein / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weightTheoretical: 134.115719 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: MGVKVLFALI CIAVAEAQCV NLTTRTQLPP AYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH AIHVSGTNGT KRFDNPVLP FNDGVYFAST EKSNIIRGWI FGTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLGVYY HKNNKSWMES E FRVYSSAN ...String:
MGVKVLFALI CIAVAEAQCV NLTTRTQLPP AYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH AIHVSGTNGT KRFDNPVLP FNDGVYFAST EKSNIIRGWI FGTTLDSKTQ SLLIVNNATN VVIKVCEFQF CNDPFLGVYY HKNNKSWMES E FRVYSSAN NCTFEYVSQP FLMDLEGKQG NFKNLREFVF KNIDGYFKIY SKHTPINLVR DLPQGFSALE PLVDLPIGIN IT RFQTLLA LHRSYLTPGD SSSGWTAGAA AYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL KSFTVEKGIY QTS NFRVQP TESIVRFPNI TNLCPFGEVF NATRFASVYA WNRKRISNCV ADYSVLYNSA SFSTFKCYGV SPTKLNDLCF TNVY ADSFV IRGDEVRQIA PGQTGKIADY NYKLPDDFTG CVIAWNSNNL DSKVGGNYNY LYRLFRKSNL KPFERDISTE IYQAG STPC NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN FNFNGLTGTG VLTESN KKF LPFQQFGRDI ADTTDAVRDP QTLEILDITP CSFGGVSVIT PGTNTSNQVA VLYQDVNCTE VPVAIHADQL TPTWRVY ST GSNVFQTRAG CLIGAEHVNN SYECDIPIGA GICASYQTQT NSPGSASSVA SQSIIAYTMS LGAENSVAYS NNSIAIPT N FTISVTTEIL PVSMTKTSVD CTMYICGDST ECSNLLLQYG SFCTQLNRAL TGIAVEQDKN TQEVFAQVKQ IYKTPPIKD FGGFNFSQIL PDPSKPSKRS FIEDLLFNKV TLADAGFIKQ YGDCLGDIAA RDLICAQKFN GLTVLPPLLT DEMIAQYTSA LLAGTITSG WTFGAGPALQ IPFPMQMAYR FNGIGVTQNV LYENQKLIAN QFNSAIGKIQ DSLSSTPSAL GKLQDVVNQN A QALNTLVK QLSSNFGAIS SVLNDILSRL DPPEAEVQID RLITGRLQSL QTYVTQQLIR AAEIRASANL AATKMSECVL GQ SKRVDFC GKGYHLMSFP QSAPHGVVFL HVTYVPAQEK NFTTAPAICH DGKAHFPREG VFVSNGTHWF VTQRNFYEPQ IIT TDNTFV SGNCDVVIGI VNNTVYDPLQ PELDSFKEEL DKYFKNHTSP DVDLGDISGI NASVVNIQKE IDRLNEVAKN LNES LIDLQ ELGKYEQ

UniProtKB: Spike glycoprotein

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Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 21 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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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 / Details: TBS buffer pH 7.4
GridModel: C-flat-2/1 / Support film - Material: GRAPHENE OXIDE / Support film - topology: CONTINUOUS
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: 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: 2.5 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v3.3.1) / Number images used: 131404
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC

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