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- PDB-6ws6: Structural and functional analysis of a potent sarbecovirus neutr... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6ws6 | |||||||||
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Title | Structural and functional analysis of a potent sarbecovirus neutralizing antibody | |||||||||
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![]() | IMMUNE SYSTEM / fusion protein / neutralizing antibody / sarbecovirus / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID | |||||||||
Function / homology | Chem-JEF![]() | |||||||||
Biological species | ![]() | |||||||||
Method | ![]() ![]() ![]() ![]() | |||||||||
![]() | Pinto, D. / Park, Y.J. / Beltramello, M. / Walls, A.C. / Tortorici, M.A. / Bianchi, S. / Jaconi, S. / Culap, K. / Zatta, F. / Marco, A.D. ...Pinto, D. / Park, Y.J. / Beltramello, M. / Walls, A.C. / Tortorici, M.A. / Bianchi, S. / Jaconi, S. / Culap, K. / Zatta, F. / Marco, A.D. / Peter, A. / Guarino, B. / Spreafico, R. / Cameroni, E. / Case, J.B. / Chen, R.E. / Havenar-Daughton, C. / Snell, G. / Telenti, A. / Virgin, H.W. / Lanzavecchia, A. / Diamond, M.S. / Fink, K. / Veesler, D. / Corti, D. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Authors: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / ...Authors: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / Barbara Guarino / Roberto Spreafico / Elisabetta Cameroni / James Brett Case / Rita E Chen / Colin Havenar-Daughton / Gyorgy Snell / Amalio Telenti / Herbert W Virgin / Antonio Lanzavecchia / Michael S Diamond / Katja Fink / David Veesler / Davide Corti / ![]() ![]() ![]() Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 2020. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease. #1: Journal: bioRxiv / Year: 2020 Title: Structural and functional analysis of a potent sarbecovirus neutralizing antibody. Authors: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / ...Authors: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / Barbara Guarino / Roberto Spreafico / Elisabetta Cameroni / James Brett Case / Rita E Chen / Colin Havenar-Daughton / Gyorgy Snell / Amalio Telenti / Herbert W Virgin / Antonio Lanzavecchia / Michael S Diamond / Katja Fink / David Veesler / Davide Corti Abstract: SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths . Vaccine and therapeutic discovery ...SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths . Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of a SARS survivor infected in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 498.6 KB | Display | ![]() |
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PDB format | ![]() | 412.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 6wpsC ![]() 6wptC ![]() 6nb8S S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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3 | ![]()
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Unit cell |
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Components
#1: Antibody | Mass: 24573.471 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Antibody | Mass: 23204.697 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Chemical | ChemComp-JEF / | Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 4.62 Å3/Da / Density % sol: 73.37 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 8 Details: 1.1 M Sodium Malonate, 0.1 M HEPES, pH 7.0 and 0.5% (w/v) Jeffamine ED-2001 |
-Data collection
Diffraction | Mean temperature: 80 K / Serial crystal experiment: N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Mar 31, 2020 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Single crystal, cylindrically bent, Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9713 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 3.3→121.355 Å / Num. all: 41395 / Num. obs: 41395 / % possible obs: 100 % / Redundancy: 11.9 % / Rpim(I) all: 0.054 / Rrim(I) all: 0.187 / Rsym value: 0.179 / Net I/av σ(I): 4.2 / Net I/σ(I): 13.2 / Num. measured all: 493741 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 6NB8 Resolution: 3.3→93.76 Å / SU ML: 0.27 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 20.09 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 219.28 Å2 / Biso mean: 77.9547 Å2 / Biso min: 31.3 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 3.3→93.76 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 15 / % reflection obs: 100 %
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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