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- PDB-7xdl: Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex wi... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7xdl | ||||||
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Title | Cryo-EM structure of SARS-CoV-2 Delta Spike protein in complex with BA7208 and BA7125 fab | ||||||
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![]() | VIRAL PROTEIN | ||||||
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: 3.08 Å | ||||||
![]() | Liu, Z. / Liu, S. / Yuanzhu, G. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5. Authors: Yanqun Wang / An Yan / Deyong Song / Chuangchuang Dong / Muding Rao / Yuanzhu Gao / Ruxi Qi / Xiaomin Ma / Qiaoping Wang / Hongguang Xu / Hong Liu / Jing Han / Maoqin Duan / Shuo Liu / ...Authors: Yanqun Wang / An Yan / Deyong Song / Chuangchuang Dong / Muding Rao / Yuanzhu Gao / Ruxi Qi / Xiaomin Ma / Qiaoping Wang / Hongguang Xu / Hong Liu / Jing Han / Maoqin Duan / Shuo Liu / Xiaoping Yu / Mengqi Zong / Jianxia Feng / Jie Jiao / Huimin Zhang / Min Li / Beibei Yu / Yanxia Wang / Fanhao Meng / Xiaodan Ni / Ying Li / Zhenduo Shen / Baiping Sun / Xin Shao / Haifeng Zhao / Yanyan Zhao / Rui Li / Yanan Zhang / Guangying Du / Jun Lu / Chunna You / Hua Jiang / Lu Zhang / Lan Wang / Changlin Dou / Zheng Liu / Jincun Zhao / ![]() Abstract: SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, ...SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1-BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 849.5 KB | Display | ![]() |
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PDB format | ![]() | 704.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 33151MC ![]() 7xczC ![]() 7xdaC ![]() 7xdbC ![]() 7xdkC 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
-Protein , 1 types, 3 molecules ABC
#1: Protein | Mass: 123251.586 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2 / Cell line (production host): HEK293 / Production host: ![]() |
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-Antibody , 4 types, 12 molecules DFHEGIJLOKMP
#2: Antibody | Mass: 22882.381 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Antibody | Mass: 22978.664 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Antibody | Mass: 11515.722 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #5: Antibody | Mass: 13397.985 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 2 types, 24 molecules ![](data/chem/img/NAG.gif)
#6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | Y |
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-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
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
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: 5000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 1.39 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.08 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 223225 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Highest resolution: 3.08 Å | ||||||||||||||||||||||||
Refine LS restraints |
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