+Open data
-Basic information
Entry | Database: PDB / ID: 8xki | |||||||||
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Title | A neutralizing nanobody VHH60 against wt SARS-CoV-2 | |||||||||
Components |
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Keywords | ANTIVIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / spike glycoprotein / virus / antibody / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex / ANTIVIRAL PROTEIN / ANTIVIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
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 / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / 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 | synthetic construct (others) Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Lu, Y. / Guo, H. / Ji, X. / Yang, H. | |||||||||
Funding support | 2items
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Citation | Journal: Cell Death Dis / Year: 2024 Title: A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug. Authors: Qianyun Liu / Yuchi Lu / Chenguang Cai / Yanyan Huang / Li Zhou / Yanbin Guan / Shiying Fu / Youyou Lin / Huan Yan / Zhen Zhang / Xiang Li / Xiuna Yang / Haitao Yang / Hangtian Guo / Ke Lan ...Authors: Qianyun Liu / Yuchi Lu / Chenguang Cai / Yanyan Huang / Li Zhou / Yanbin Guan / Shiying Fu / Youyou Lin / Huan Yan / Zhen Zhang / Xiang Li / Xiuna Yang / Haitao Yang / Hangtian Guo / Ke Lan / Yu Chen / Shin-Chen Hou / Yi Xiong / Abstract: SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven ...SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S, Sand S as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8xki.cif.gz | 559.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8xki.ent.gz | 448.5 KB | Display | PDB format |
PDBx/mmJSON format | 8xki.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8xki_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 8xki_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8xki_validation.xml.gz | 92.7 KB | Display | |
Data in CIF | 8xki_validation.cif.gz | 138.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xk/8xki ftp://data.pdbj.org/pub/pdb/validation_reports/xk/8xki | HTTPS FTP |
-Related structure data
Related structure data | 38418MC 8xk2C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Antibody | Mass: 13410.872 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) | ||||||
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#2: Protein | Mass: 142347.281 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #3: 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 #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 |
-Sample preparation
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 207363 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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