|Entry||Database: EMDB / ID: EMD-23160|
|Title||Prefusion-stabilized SARS-CoV-2 spike bound by the engineered human antibody ADG-2|
|Sample||Prefusion-stabilized SARS-CoV-2 spike bound by a single copy of ADG-2 Fab:|
ADG-2 Fab / spike glycoproteinPeplomer
|Biological species||Homo sapiens (human) / Severe acute respiratory syndrome coronavirus 2|
|Method||single particle reconstruction / cryo EM / Resolution: 5.94 Å|
|Authors||Wrapp D / McLellan JS|
|Funding support|| United States, 1 items |
|Citation||Journal: Science / Year: 2021|
Title: Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.
Authors: C Garrett Rappazzo / Longping V Tse / Chengzi I Kaku / Daniel Wrapp / Mrunal Sakharkar / Deli Huang / Laura M Deveau / Thomas J Yockachonis / Andrew S Herbert / Michael B Battles / Cecilia M ...Authors: C Garrett Rappazzo / Longping V Tse / Chengzi I Kaku / Daniel Wrapp / Mrunal Sakharkar / Deli Huang / Laura M Deveau / Thomas J Yockachonis / Andrew S Herbert / Michael B Battles / Cecilia M O'Brien / Michael E Brown / James C Geoghegan / Jonathan Belk / Linghang Peng / Linlin Yang / Yixuan Hou / Trevor D Scobey / Dennis R Burton / David Nemazee / John M Dye / James E Voss / Bronwyn M Gunn / Jason S McLellan / Ralph S Baric / Lisa E Gralinski / Laura M Walker /
Abstract: The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three ...The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses.
|Validation Report||Summary, Full report, XML, About validation report|
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_23160.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 1.047 Å|
|Symmetry||Space group: 1|
CCP4 map header:
-Half map: Half map A
|Annotation||Half map A|
|Projections & Slices|
-Half map: Half map B
-Entire Prefusion-stabilized SARS-CoV-2 spike bound by a single copy of A...
|Entire||Name: Prefusion-stabilized SARS-CoV-2 spike bound by a single copy of ADG-2 Fab|
Number of components: 3
-Component #1: protein, Prefusion-stabilized SARS-CoV-2 spike bound by a single ...
|Protein||Name: Prefusion-stabilized SARS-CoV-2 spike bound by a single copy of ADG-2 Fab|
Recombinant expression: No
|Mass||Theoretical: 500 kDa|
-Component #2: protein, ADG-2 Fab
|Protein||Name: ADG-2 Fab / Recombinant expression: No|
|Source||Species: Homo sapiens (human)|
|Source (engineered)||Expression System: Homo sapiens (human)|
-Component #3: protein, spike glycoprotein
|Protein||Name: spike glycoproteinPeplomer / Recombinant expression: No|
|Source||Species: Severe acute respiratory syndrome coronavirus 2|
|Source (engineered)||Expression System: unidentified (others)|
|Specimen||Specimen state: Particle / Method: cryo EM|
|Sample solution||Specimen conc.: 0.35 mg/mL / pH: 8|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Temperature: 278 K / Humidity: 100 % / Details: Blotted for 6 seconds at -1 force.|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Imaging||Microscope: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 36 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Processing||Method: single particle reconstruction / Applied symmetry: C1 (asymmetric) / Number of projections: 57078|
|3D reconstruction||Software: cryoSPARC / Resolution: 5.94 Å / Resolution method: FSC 0.143 CUT-OFF|
|FSC plot (resolution estimation)|
-Atomic model buiding
|Modeling #1||Input PDB model: 6XKL|
-Aug 12, 2020. New: Covid-19 info
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Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data
-Mar 5, 2020. Novel coronavirus structure data
Novel coronavirus structure data
- International Committee on Taxonomy of Viruses (ICTV) defined the short name of the 2019 coronavirus as "SARS-CoV-2".
The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 - nature microbiology
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