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- EMDB-35039: SARS-CoV2 spike protein with ACE2 decoy. 2 ACE2 decoy bound form. -

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Basic information

Entry
Database: EMDB / ID: EMD-35039
TitleSARS-CoV2 spike protein with ACE2 decoy. 2 ACE2 decoy bound form.
Map dataspike, 2 ACE2 decoy, 2 up
Sample
  • Complex: SARS-CoV2 spike protein with ACE2 decoy. 2 ACE2 decoy bound form.
KeywordsSARS-CoV2 / spike protein / ACE2 / ACE2 decoy / VIRAL PROTEIN
Biological speciesSevere acute respiratory syndrome coronavirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsKishikawa J / Hirose M / Kato T / Okamoto T
Funding support Japan, 5 items
OrganizationGrant numberCountry
Japan Agency for Medical Research and Development (AMED)JP21fk0108465 Japan
Japan Agency for Medical Research and Development (AMED)JP21fk0108481 Japan
Japan Agency for Medical Research and Development (AMED)JP21wm0325009 Japan
Japan Agency for Medical Research and Development (AMED)JP22wm0325009 Japan
Japan Agency for Medical Research and Development (AMED)JP21am0101075 Japan
CitationJournal: Sci Transl Med / Year: 2023
Title: An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models.
Authors: Emiko Urano / Yumi Itoh / Tatsuya Suzuki / Takanori Sasaki / Jun-Ichi Kishikawa / Kanako Akamatsu / Yusuke Higuchi / Yusuke Sakai / Tomotaka Okamura / Shuya Mitoma / Fuminori Sugihara / ...Authors: Emiko Urano / Yumi Itoh / Tatsuya Suzuki / Takanori Sasaki / Jun-Ichi Kishikawa / Kanako Akamatsu / Yusuke Higuchi / Yusuke Sakai / Tomotaka Okamura / Shuya Mitoma / Fuminori Sugihara / Akira Takada / Mari Kimura / Shuto Nakao / Mika Hirose / Tadahiro Sasaki / Ritsuko Koketsu / Shunya Tsuji / Shota Yanagida / Tatsuo Shioda / Eiji Hara / Satoaki Matoba / Yoshiharu Matsuura / Yasunari Kanda / Hisashi Arase / Masato Okada / Junichi Takagi / Takayuki Kato / Atsushi Hoshino / Yasuhiro Yasutomi / Akatsuki Saito / Toru Okamoto /
Abstract: The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron ...The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity ACE2 and an IgG1 Fc domain could offer an alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum and therapeutic potential in rodent models. Here, we demonstrate that the engineered ACE2 decoy retains neutralization activity against Omicron subvariants, including the currently emerging XBB and BQ.1 strains, which completely evade antibodies currently in clinical use. SARS-CoV-2, under the suboptimal concentration of neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against the engineered ACE2 decoy. Furthermore, inhalation of aerosolized decoys improved the outcomes of rodents infected with SARS-CoV-2 at a 20-fold lower dose than that of intravenous administration. Last, the engineered ACE2 decoy exhibited therapeutic efficacy for cynomolgus macaques infected with SARS-CoV-2. These results indicate that this engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation could be considered as a noninvasive approach to enhance the efficacy of COVID-19 treatments.
History
DepositionDec 23, 2022-
Header (metadata) releaseDec 27, 2023-
Map releaseDec 27, 2023-
UpdateDec 27, 2023-
Current statusDec 27, 2023Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_35039.png

Downloads & links

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Map

FileDownload / File: emd_35039.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationspike, 2 ACE2 decoy, 2 up
Voxel sizeX=Y=Z: 1.17 Å
Density
Contour LevelBy AUTHOR: 0.19
Minimum - Maximum-0.87422115 - 1.5767734
Average (Standard dev.)0.0001487827 (±0.039519913)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 351.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_35039_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_35039_half_map_1.map
Annotationhalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map A

Fileemd_35039_half_map_2.map
Annotationhalf map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : SARS-CoV2 spike protein with ACE2 decoy. 2 ACE2 decoy bound form.

EntireName: SARS-CoV2 spike protein with ACE2 decoy. 2 ACE2 decoy bound form.
Components
  • Complex: SARS-CoV2 spike protein with ACE2 decoy. 2 ACE2 decoy bound form.

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Supramolecule #1: SARS-CoV2 spike protein with ACE2 decoy. 2 ACE2 decoy bound form.

SupramoleculeName: SARS-CoV2 spike protein with ACE2 decoy. 2 ACE2 decoy bound form.
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weightTheoretical: 460 KDa

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
Component:
ConcentrationNameFormula
20.0 mMTris
250.0 mMsodium chlorideNaClSodium chloride
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 0.085 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 7947 / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 880910
Startup modelType of model: INSILICO MODEL / In silico model: cryosparc ab initio reconstruction
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationNumber classes: 3 / Avg.num./class: 171457 / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 272706
FSC plot (resolution estimation)

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