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Open data
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Basic information
Entry | Database: PDB / ID: 8d8r | ||||||
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Title | SARS-CoV-2 Spike RBD in complex with DMAb 2196 | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / SARS-CoV-2 / Spike / RBD / IgG / DMAb / antibody cocktail / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | ||||||
![]() | Du, J. / Cui, J. / Pallesen, J. | ||||||
Funding support | ![]()
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![]() | ![]() Title: DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2. Authors: Elizabeth M Parzych / Jianqiu Du / Ali R Ali / Katherine Schultheis / Drew Frase / Trevor R F Smith / Jiayan Cui / Neethu Chokkalingam / Nicholas J Tursi / Viviane M Andrade / Bryce M Warner ...Authors: Elizabeth M Parzych / Jianqiu Du / Ali R Ali / Katherine Schultheis / Drew Frase / Trevor R F Smith / Jiayan Cui / Neethu Chokkalingam / Nicholas J Tursi / Viviane M Andrade / Bryce M Warner / Ebony N Gary / Yue Li / Jihae Choi / Jillian Eisenhauer / Igor Maricic / Abhijeet Kulkarni / Jacqueline D Chu / Gabrielle Villafana / Kim Rosenthal / Kuishu Ren / Joseph R Francica / Sarah K Wootton / Pablo Tebas / Darwyn Kobasa / Kate E Broderick / Jean D Boyer / Mark T Esser / Jesper Pallesen / Dan W Kulp / Ami Patel / David B Weiner / ![]() ![]() Abstract: Monoclonal antibody therapy has played an important role against SARS-CoV-2. Strategies to deliver functional, antibody-based therapeutics with improved in vivo durability are needed to supplement ...Monoclonal antibody therapy has played an important role against SARS-CoV-2. Strategies to deliver functional, antibody-based therapeutics with improved in vivo durability are needed to supplement current efforts and reach underserved populations. Here, we compare recombinant mAbs COV2-2196 and COV2-2130, which compromise clinical cocktail Tixagevimab/Cilgavimab, with optimized nucleic acid-launched forms. Functional profiling of in vivo-expressed, DNA-encoded monoclonal antibodies (DMAbs) demonstrated similar specificity, broad antiviral potency and equivalent protective efficacy in multiple animal challenge models of SARS-CoV-2 prophylaxis compared to protein delivery. In PK studies, DNA-delivery drove significant serum antibody titers that were better maintained compared to protein administration. Furthermore, cryo-EM studies performed on serum-derived DMAbs provide the first high-resolution visualization of in vivo-launched antibodies, revealing new interactions that may promote cooperative binding to trimeric antigen and broad activity against VoC including Omicron lineages. These data support the further study of DMAb technology in the development and delivery of valuable biologics. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 118 KB | Display | ![]() |
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PDB format | ![]() | 78.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27255MC ![]() 8d8qC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Antibody | Mass: 23574.102 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Antibody | Mass: 24166.238 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 131573.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Strain: human/USA/WA-CDC-WA1/2020USA_WA1/2020 / Gene: S, 2 / Production host: ![]() |
#4: Sugar | ChemComp-NAG / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: SARS-CoV-2 Spike RBD in complex with DMAb 2196 / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 0.7 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 400 nm |
Image recording | Electron dose: 42.969 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 192478 / Symmetry type: POINT |