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- PDB-7z0x: THSC20.HVTR26 Fab bound to SARS-CoV-2 Receptor Binding Domain -

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Basic information

Entry
Database: PDB / ID: 7z0x
TitleTHSC20.HVTR26 Fab bound to SARS-CoV-2 Receptor Binding Domain
Components
  • (THSC20.HVTR26 Fab ...) x 2
  • Spike protein S1
KeywordsANTIVIRAL PROTEIN / Neutralizing antibody / SARS-CoV-2 / Spike / RBD / IMMUNOLOGY
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 / suppression by virus 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 / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / 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 / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Betacoronavirus spike glycoprotein S1, receptor binding / 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
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsWibmer, C.K.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/John E. Fogarty International Center (NIH/FIC)3R21TW011454-02S1 United States
Citation
Journal: 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.
#1: Journal: Biorxiv / Year: 2021
Title: A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 delta variant
Authors: Hingankar, N. / Deshpande, S. / Das, P. / Rizvi, Z.A. / Burns, A. / Barman, S. / Zhao, F. / Ansari, M.Y. / Mukherjee, S. / Torres, J.L. / Chattopadhyay, S. / Mehdi, F. / Sutar, J. / Rathore, ...Authors: Hingankar, N. / Deshpande, S. / Das, P. / Rizvi, Z.A. / Burns, A. / Barman, S. / Zhao, F. / Ansari, M.Y. / Mukherjee, S. / Torres, J.L. / Chattopadhyay, S. / Mehdi, F. / Sutar, J. / Rathore, D.K. / Pargai, K. / Singh, J. / Sonar, S. / Jakhar, K. / Bhattacharyya, S. / Mani, S. / Singh, S. / Dandotiya, J. / Kshetrapal, P. / Thiruvengadam, R. / Batra, G. / Medigeshi, G. / Ward, A.B. / Bhatnagar, S. / Awasthi, A. / Sok, D. / Bhattacharya, J.
History
DepositionFeb 23, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 13, 2022Provider: repository / Type: Initial release
Revision 1.1May 11, 2022Group: Database references / Source and taxonomy / Structure summary
Category: citation / citation_author ...citation / citation_author / entity / entity_src_gen / struct_ref / struct_ref_seq / struct_ref_seq_dif
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation_author.identifier_ORCID / _entity.pdbx_description / _entity_src_gen.pdbx_gene_src_gene / _struct_ref.db_code / _struct_ref.pdbx_align_begin / _struct_ref.pdbx_db_accession / _struct_ref_seq.db_align_beg / _struct_ref_seq.db_align_end / _struct_ref_seq.pdbx_db_accession / _struct_ref_seq_dif.pdbx_seq_db_accession_code
Revision 1.2May 1, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / pdbx_initial_refinement_model
Item: _citation.journal_id_ISSN
Revision 1.3Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: THSC20.HVTR26 Fab heavy chain
L: THSC20.HVTR26 Fab light chain
R: Spike protein S1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,5585
Polymers70,7493
Non-polymers8092
Water10,935607
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)90.286, 104.213, 89.064
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212

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Components

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Antibody , 2 types, 2 molecules HL

#1: Antibody THSC20.HVTR26 Fab heavy chain


Mass: 24876.953 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Donor THSC20 / Source: (gene. exp.) Homo sapiens (human) / Tissue: Blood / Cell: B cell / Plasmid: pcDNA3.4 / Cell line (production host): Expi293 / Production host: Homo sapiens (human)
#2: Antibody THSC20.HVTR26 Fab light chain


Mass: 22856.252 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Donor THSC20 / Source: (gene. exp.) Homo sapiens (human) / Tissue: Blood / Cell: B cell / Plasmid: pcDNA3.4 / Cell line (production host): Expi293 / Production host: Homo sapiens (human)

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Protein / Sugars , 2 types, 2 molecules R

#3: Protein Spike protein S1


Mass: 23015.803 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: 11th resolved amino acid (annotated as position N343) is linked to glycan (NAG-NAG-FUC). Last seven amino acids (GLEVLFQ) - protease cleavage site used to remove purification tag. Can still ...Details: 11th resolved amino acid (annotated as position N343) is linked to glycan (NAG-NAG-FUC). Last seven amino acids (GLEVLFQ) - protease cleavage site used to remove purification tag. Can still be labelled as 'expression tags'.
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Gene: S, 2 / Variant: None / Plasmid: pcDNA3.4 / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2
#4: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 570.542 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4[LFucpa1-6]DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-1-2/a4-b1_a6-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}[(6+1)][a-L-Fucp]{}}LINUCSPDB-CARE

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Non-polymers , 2 types, 608 molecules

#5: Chemical ChemComp-EPE / 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / HEPES


Mass: 238.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H18N2O4S / Comment: pH buffer*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 607 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.96 Å3/Da / Density % sol: 58.45 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion / pH: 7
Details: 15% (w/v) PEG 20,000, 100 mM HEPES / Sodium hydroxide pH 7.0
Temp details: Constant

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Feb 11, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 1.8→50 Å / Num. obs: 72244 / % possible obs: 92 % / Redundancy: 2 % / Biso Wilson estimate: 26.54 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.01945 / Rpim(I) all: 0.01945 / Rrim(I) all: 0.0275 / Net I/σ(I): 20.3
Reflection shellResolution: 1.8→1.86 Å / Redundancy: 2 % / Rmerge(I) obs: 0.3089 / Mean I/σ(I) obs: 2 / Num. unique obs: 72238 / CC1/2: 0.727 / Rpim(I) all: 0.3089 / Rrim(I) all: 0.4368 / % possible all: 50

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Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
XSCALEdata scaling
PDB_EXTRACT3.27data extraction
autoPROCdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: AlphaFold

Resolution: 1.8→50 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 18.15 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1875 3530 4.88 %
Rwork0.1625 68736 -
obs0.1638 72238 91.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 153.76 Å2 / Biso mean: 51.4874 Å2 / Biso min: 13.53 Å2
Refinement stepCycle: final / Resolution: 1.8→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4794 0 93 607 5494
Biso mean--62.97 41.45 -
Num. residues----634
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 25

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.8-1.820.3063520.28431109116138
1.82-1.850.2839910.24341600169154
1.85-1.880.2578800.22491968204866
1.88-1.910.24021000.20952293239377
1.91-1.940.21971270.20472447257483
1.94-1.970.24981330.192599273288
1.97-2.010.19861280.18112779290793
2.01-2.050.19991640.18082907307199
2.05-2.090.21121410.180229483089100
2.09-2.130.191580.177829623120100
2.13-2.180.20641780.177129383116100
2.18-2.240.21441430.169929563099100
2.24-2.30.1911210.16730223143100
2.3-2.370.17481520.167529693121100
2.37-2.440.20981800.160929583138100
2.44-2.530.20111800.159729413121100
2.53-2.630.2131520.160429883140100
2.63-2.750.18221550.166529883143100
2.75-2.890.19081780.166629803158100
2.89-3.080.16521440.157330003144100
3.08-3.310.17671480.156330073155100
3.31-3.650.19041380.151430693207100
3.65-4.170.19571490.143630393188100
4.17-5.260.13051930.126130453238100
5.26-45.140.21241450.188632243369100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.4091-0.34910.13461.60630.65662.121-0.04450.26160.1541-0.28930.0158-0.1556-0.12450.15670.00140.1842-0.04390.030.2210.02850.1755-8.27427.0125-17.2422
20.5302-0.5543-0.01340.61550.3110.47490.18390.1740.5168-0.22460.3432-0.26620.0836-0.02440.03280.9540.07610.10960.80010.28910.7135-20.717328.4767-47.2084
32.31861.384-0.07951.7510.49291.924-0.10090.19960.477-0.14180.0210.3485-0.261-0.225-0.00550.1690.0167-0.03440.16480.01770.2521-27.874931.6024-10.6727
41.26-0.48370.09650.3134-0.29560.60580.15310.2922-0.407-0.2381-0.22430.29180.3108-0.4463-00.9594-0.0574-0.11641.1170.3210.8009-35.895222.0595-46.0048
52.36030.35870.41651.5970.19421.09760.014-0.09820.27410.0196-0.0224-0.1296-0.11770.078-0.00230.16620.0222-0.01030.1429-0.02720.161816.335847.43788.7619
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'H' and (resid 1 through 113 )H1 - 113
2X-RAY DIFFRACTION2chain 'H' and (resid 114 through 216 )H114 - 216
3X-RAY DIFFRACTION3chain 'L' and (resid 1 through 108 )L1 - 108
4X-RAY DIFFRACTION4chain 'L' and (resid 109 through 211 )L109 - 211
5X-RAY DIFFRACTION5chain 'R' and (resid 333 through 527 )R333 - 527

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