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- PDB-8h3e: Complex structure of a small molecule (SPC-14) bound SARS-CoV-2 s... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8h3e | ||||||
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Title | Complex structure of a small molecule (SPC-14) bound SARS-CoV-2 spike protein, closed state | ||||||
![]() | Spike glycoprotein,Fibritin | ||||||
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Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Meng, F. / Wang, Q. / Xie, Y. / Ni, X. / Huang, N. | ||||||
Funding support | ![]()
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![]() | ![]() Title: In Silico Discovery of Small Molecule Modulators Targeting the Achilles' Heel of SARS-CoV-2 Spike Protein. Authors: Qing Wang / Fanhao Meng / Yuting Xie / Wei Wang / Yumin Meng / Linjie Li / Tao Liu / Jianxun Qi / Xiaodan Ni / Sanduo Zheng / Jianhui Huang / Niu Huang / ![]() Abstract: The spike protein of SARS-CoV-2 has been a promising target for developing vaccines and therapeutics due to its crucial role in the viral entry process. Previously reported cryogenic electron ...The spike protein of SARS-CoV-2 has been a promising target for developing vaccines and therapeutics due to its crucial role in the viral entry process. Previously reported cryogenic electron microscopy (cryo-EM) structures have revealed that free fatty acids (FFA) bind with SARS-CoV-2 spike protein, stabilizing its closed conformation and reducing its interaction with the host cell target in vitro. Inspired by these, we utilized a structure-based virtual screening approach against the conserved FFA-binding pocket to identify small molecule modulators of SARS-CoV-2 spike protein, which helped us identify six hits with micromolar binding affinities. Further evaluation of their commercially available and synthesized analogs enabled us to discover a series of compounds with better binding affinities and solubilities. Notably, our identified compounds exhibited similar binding affinities against the spike proteins of the prototypic SARS-CoV-2 and a currently circulating Omicron BA.4 variant. Furthermore, the cryo-EM structure of the compound SPC-14 bound spike revealed that SPC-14 could shift the conformational equilibrium of the spike protein toward the closed conformation, which is human ACE2 (hACE2) inaccessible. Our identified small molecule modulators targeting the conserved FFA-binding pocket could serve as the starting point for the future development of broad-spectrum COVID-19 intervention treatments. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 639.4 KB | Display | ![]() |
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PDB format | ![]() | 527.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 34465MC ![]() 8h3dC 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
#1: Protein | Mass: 141338.359 Da / Num. of mol.: 3 / Fragment: SARS-CoV-2 spike protein,SARS-CoV-2 spike protein / Mutation: R682S,R683G,R685G,K986P,V987P Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() Gene: S, 2, wac / Plasmid: pcDNA3 / Production host: ![]() ![]() #2: Chemical | #3: Sugar | ChemComp-NAG / ![]() Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Complex of SARS-CoV-2 spike protein and a small molecule (SPC-14) Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||
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Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() ![]() | ||||||||||||
Buffer solution | pH: 8 | ||||||||||||
Buffer component | Conc.: 20 mM / Name: HEPES![]() | ||||||||||||
Specimen | Conc.: 1.53 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K |
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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![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 4841 |
Image scans | Width: 4096 / Height: 4096 |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.06 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 59187 / Num. of class averages: 1 / Symmetry type: POINT |