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- EMDB-67548: Cryo-EM map of SARS-CoV-2 BA.2.75 Spike Protein complex with a ma... -

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Basic information

Entry
Database: EMDB / ID: EMD-67548
TitleCryo-EM map of SARS-CoV-2 BA.2.75 Spike Protein complex with a macrocyclic peptide 6L3-3P11K (Two RBDs up)
Map data
Sample
  • Complex: BA.2.75 S/6L3 (Two RBDs up)
Keywordsreceptor binding / VIRAL PROTEIN
Biological speciesSevere acute respiratory syndrome coronavirus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsWang M / Peng Q / Yang JY / Shi Y
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32192452 China
CitationJournal: Nat Commun / Year: 2026
Title: Intranasal administration of broad-spectrum macrocyclic peptide inhibitor protects against SARS-CoV-2 Omicron variants.
Authors: Min Wang / Jinyue Yang / Yahong Tan / Shuofeng Yuan / Guoli Shi / Qi Peng / Yongqi Li / Vincent Kwok-Man Poon / Chris Chung-Sing Chan / Na Xiao / Anna Jinxia Zhang / Yubin Xie / Junhua Li / ...Authors: Min Wang / Jinyue Yang / Yahong Tan / Shuofeng Yuan / Guoli Shi / Qi Peng / Yongqi Li / Vincent Kwok-Man Poon / Chris Chung-Sing Chan / Na Xiao / Anna Jinxia Zhang / Yubin Xie / Junhua Li / Hao Luo / Yaning Fu / Yong Chen / Alex A Compton / Youming Zhang / Yang Yang / George Fu Gao / Hongwei Hou / Jasper Fuk-Woo Chan / Yizhen Yin / Yi Shi /
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause significant morbidity and mortality despite the end of its pandemic phase. The emergence of highly mutated SARS-CoV-2 ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause significant morbidity and mortality despite the end of its pandemic phase. The emergence of highly mutated SARS-CoV-2 variants of concern highlights the requirement of broad-spectrum antiviral countermeasures which possess both prophylactic and therapeutic efficacies. Here, we obtain a macrocyclic peptide, 6L3-3P11K, that effectively inhibits a wide range of SARS-CoV-2 variants and subvariants. Structural studies show that 6L3-3P11K forms homotrimers that lock the spike protein (S) trimer into a "closed" conformation by engaging a conserved non-receptor binding motif (non-RBM) of S. This interaction disrupts the binding between S and ACE2 receptor. Structure-guided modifications result in a thermostable and trypsin-resistant macrocyclic peptide, 6L3-1F3P11hR, that exhibits prophylactic and therapeutic effects against SARS-CoV-2 infection in a male hACE2 transgenic mouse model after intranasal administration. Our results provide a drug candidate for the control and prevention of COVID-19 and may stimulate further research on macrocyclic broad-spectrum anti-coronavirus drug development.
History
DepositionDec 5, 2025-
Header (metadata) releaseMar 11, 2026-
Map releaseMar 11, 2026-
UpdateMar 11, 2026-
Current statusMar 11, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_67548.png

Downloads & links

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Map

FileDownload / File: emd_67548.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.71 Å/pix.
x 480 pix.
= 340.8 Å		0.71 Å/pix.
x 480 pix.
= 340.8 Å		0.71 Å/pix.
x 480 pix.
= 340.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.71 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.112
Minimum - Maximum-0.18281417 - 0.57960355
Average (Standard dev.)-0.0014201051 (±0.018599216)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 340.8 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_67548_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_67548_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : BA.2.75 S/6L3 (Two RBDs up)

EntireName: BA.2.75 S/6L3 (Two RBDs up)
Components
  • Complex: BA.2.75 S/6L3 (Two RBDs up)

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Supramolecule #1: BA.2.75 S/6L3 (Two RBDs up)

SupramoleculeName: BA.2.75 S/6L3 (Two RBDs up) / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Severe acute respiratory syndrome coronavirus

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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
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.5 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 136369
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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