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Open data
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Basic information
Entry | Database: PDB / ID: 7oap | |||||||||
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Title | Nanobody H3 AND C1 bound to RBD | |||||||||
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![]() | ANTIVIRAL PROTEIN / RBD / nanobody / high affinity | |||||||||
Function / homology | ![]() 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 / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / 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 | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Naismith, J.H. / Mikolajek, H. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19. Authors: Jiandong Huo / Halina Mikolajek / Audrey Le Bas / Jordan J Clark / Parul Sharma / Anja Kipar / Joshua Dormon / Chelsea Norman / Miriam Weckener / Daniel K Clare / Peter J Harrison / Julia A ...Authors: Jiandong Huo / Halina Mikolajek / Audrey Le Bas / Jordan J Clark / Parul Sharma / Anja Kipar / Joshua Dormon / Chelsea Norman / Miriam Weckener / Daniel K Clare / Peter J Harrison / Julia A Tree / Karen R Buttigieg / Francisco J Salguero / Robert Watson / Daniel Knott / Oliver Carnell / Didier Ngabo / Michael J Elmore / Susan Fotheringham / Adam Harding / Lucile Moynié / Philip N Ward / Maud Dumoux / Tessa Prince / Yper Hall / Julian A Hiscox / Andrew Owen / William James / Miles W Carroll / James P Stewart / James H Naismith / Raymond J Owens / ![]() ![]() ![]() ![]() ![]() Abstract: SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain ...SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four nanobodies (C5, H3, C1, F2) engineered as homotrimers with pmolar affinity for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Crystal structures show C5 and H3 overlap the ACE2 epitope, whilst C1 and F2 bind to a different epitope. Cryo Electron Microscopy shows C5 binding results in an all down arrangement of the Spike protein. C1, H3 and C5 all neutralize the Victoria strain, and the highly transmissible Alpha (B.1.1.7 first identified in Kent, UK) strain and C1 also neutralizes the Beta (B.1.35, first identified in South Africa). Administration of C5-trimer via the respiratory route showed potent therapeutic efficacy in the Syrian hamster model of COVID-19 and separately, effective prophylaxis. The molecule was similarly potent by intraperitoneal injection. #1: ![]() Title: A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19 Authors: Huo, J. / Mikolajek, H. / Le Bas, A. / Clark, J. / Sharma, P. / Kipar, A. / Dormon, J. / Norman, C. / Weckener, M. / Clare, D. / Harrison, P. / Tree, J. / Buttigieg, K. / Salguero, F. / ...Authors: Huo, J. / Mikolajek, H. / Le Bas, A. / Clark, J. / Sharma, P. / Kipar, A. / Dormon, J. / Norman, C. / Weckener, M. / Clare, D. / Harrison, P. / Tree, J. / Buttigieg, K. / Salguero, F. / Watson, R. / Knott, D. / Carnell, O. / Ngabo, D. / Elmore, M. / Fotheringham, S. / Harding, A. / Ward, P. / Moynie, L. / Dumoux, M. / Hall, Y. / Hiscox, J. / Owen, A. / James, W. / Carroll, M. / Stewart, J. / Naismith, J. / Owens, R. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 189.8 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7oanC ![]() 7oaoC ![]() 7oaqC ![]() 7oauC ![]() 7oayC ![]() 6zbpS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components on special symmetry positions |
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Components
-Antibody , 2 types, 2 molecules AAAFFF
#1: Antibody | Mass: 14659.114 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#3: Antibody | Mass: 15134.849 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-Protein / Sugars , 2 types, 2 molecules EEE![](data/chem/img/NAG.gif)
![](data/chem/img/NAG.gif)
#2: Protein | Mass: 23619.461 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2 / Production host: ![]() |
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#4: Sugar | ChemComp-NAG / |
-Non-polymers , 3 types, 237 molecules ![](data/chem/img/CIT.gif)
![](data/chem/img/CL.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/CL.gif)
![](data/chem/img/HOH.gif)
#5: Chemical | ChemComp-CIT / |
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#6: Chemical | ChemComp-CL / |
#7: Water | ChemComp-HOH / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.94 Å3/Da / Density % sol: 58.18 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 1.0 M Lithium chloride, 0.1 M Citrate pH 4, 20 % Peg 6000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 16, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9762 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→62.254 Å / Num. obs: 50645 / % possible obs: 100 % / Redundancy: 25.4 % / CC1/2: 0.99 / Rpim(I) all: 0.025 / Net I/σ(I): 14.4 |
Reflection shell | Resolution: 1.9→1.95 Å / Redundancy: 22.1 % / Mean I/σ(I) obs: 0.7 / Num. unique obs: 3478 / CC1/2: 0.94 / % possible all: 100 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 6ZBP Resolution: 1.901→62.254 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.958 / SU B: 6.988 / SU ML: 0.099 / Cross valid method: FREE R-VALUE / ESU R: 0.119 / ESU R Free: 0.111 Details: Hydrogens have been added in their riding positions
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Solvent computation | Ion probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1 Å / Solvent model: MASK BULK SOLVENT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 44.25 Å2
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Refinement step | Cycle: LAST / Resolution: 1.901→62.254 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20
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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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