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- PDB-7cab: Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by... -

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Entry
Database: PDB / ID: 7cab
TitleStructural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
ComponentsSARS-CoV-2 Spike glycoprotein
KeywordsVIRAL PROTEIN / SARS-CoV-2 / Spike glycoprotein
Function / homology
Function and homology information


suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / host cell surface receptor binding / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / suppression by virus of host type I interferon-mediated signaling pathway / viral entry into host cell / fusion of virus membrane with host endosome membrane / viral envelope ...suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated virion attachment to host cell / host cell surface receptor binding / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / suppression by virus of host type I interferon-mediated signaling pathway / viral entry into host cell / fusion of virus membrane with host endosome membrane / viral envelope / pathogenesis / host cell plasma membrane / virion membrane / integral component of membrane / identical protein binding
Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Spike glycoprotein, heptad repeat 2, coronavirus / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S1, C-terminal / Spike receptor binding domain superfamily, coronavirus / Betacoronavirus-like spike glycoprotein S1, N-terminal / Betacoronavirus spike glycoprotein S1, receptor binding
Spike glycoprotein / polysac:dglcpnacb1-4dglcpnacb1-roh:
Biological speciesSevere acute respiratory syndrome coronavirus 2
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.52 Å
AuthorsZhe, L. / Cao, L. / Deng, Y. / Sun, Y. / Wang, N. / Xie, L. / Wang, Y. / Rao, Z. / Qin, C. / Wang, X.
CitationJournal: Science / Year: 2020
Title: Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody.
Authors: Zhe Lv / Yong-Qiang Deng / Qing Ye / Lei Cao / Chun-Yun Sun / Changfa Fan / Weijin Huang / Shihui Sun / Yao Sun / Ling Zhu / Qi Chen / Nan Wang / Jianhui Nie / Zhen Cui / Dandan Zhu / Neil ...Authors: Zhe Lv / Yong-Qiang Deng / Qing Ye / Lei Cao / Chun-Yun Sun / Changfa Fan / Weijin Huang / Shihui Sun / Yao Sun / Ling Zhu / Qi Chen / Nan Wang / Jianhui Nie / Zhen Cui / Dandan Zhu / Neil Shaw / Xiao-Feng Li / Qianqian Li / Liangzhi Xie / Youchun Wang / Zihe Rao / Cheng-Feng Qin / Xiangxi Wang /
Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved ...The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.
Validation Report
SummaryFull reportAbout validation report
History
DepositionJun 8, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 16, 2020Provider: repository / Type: Initial release

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Structure visualization

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Assembly

Deposited unit
A: SARS-CoV-2 Spike glycoprotein
B: SARS-CoV-2 Spike glycoprotein
C: SARS-CoV-2 Spike glycoprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)414,83948
Polymers401,8373
Non-polymers13,00245
Water0
1


TypeNameSymmetry operationNumber
identity operation1_5551
Buried area49810 Å2
ΔGint12 kcal/mol
Surface area129810 Å2

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Components

#1: Protein SARS-CoV-2 Spike glycoprotein / S glycoprotein / E2 / Peplomer protein


Mass: 133945.516 Da / Num. of mol.: 3 / Fragment: UNP residues 1-1208
Mutation: R682G, R683S, R685S, K835M, T844M, A846Y, D848A, L849M, I850Q, C851M, Q853Y, K854R K986P, V987P
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Gene: S, 2 / Cell line (production host): HEK293T / Production host: Homo sapiens (human) / References: UniProt: P0DTC2
#2: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 15
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#3: Sugar...
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 30
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6 / Feature type: SUBJECT OF INVESTIGATION
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: SARS-CoV-2 spike glycoprotein trimer / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Source (recombinant)Organism: Homo sapiens (human) / Cell: HEK293T
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 60 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.10.1_2155: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.52 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 273158 / Symmetry type: POINT
Refine LS restraints
Refinement-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.01225639
ELECTRON MICROSCOPYf_angle_d0.89835001
ELECTRON MICROSCOPYf_dihedral_angle_d8.22720262
ELECTRON MICROSCOPYf_chiral_restr0.0584113
ELECTRON MICROSCOPYf_plane_restr0.0054464

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