6LQD

Structure of Enterovirus 71 in complex with NLD-22


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.26 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Design, Synthesis, and Evaluation of Novel Enterovirus 71 Inhibitors as Therapeutic Drug Leads for the Treatment of Human Hand, Foot, and Mouth Disease.

Zhang, M.Wang, Y.He, W.Sun, Y.Guo, Y.Zhong, W.Gao, Q.Liao, M.Wang, X.Cai, Y.Guo, Y.Rao, Z.

(2020) J Med Chem 63: 1233-1244

  • DOI: https://doi.org/10.1021/acs.jmedchem.9b01414
  • Primary Citation of Related Structures:  
    6LQD

  • PubMed Abstract: 

    Human hand, foot, and mouth disease (HFMD) is a serious public health threat with high infection rates in children and infants who reside in Asia and the Pacific regions, and no effective drugs are currently available. Enterovirus 71 (EV71) and coxsackievirus A16 are the major etiological pathogens. Based on an essential hydrophobic pocket on the viral capsid protein VP1, we designed and synthesized a series of small molecular weight compounds as inhibitors of EV71. A potential drug candidate named NLD-22 exhibited excellent antiviral activity (with an EC 50 of 5.056 nM and a 100% protection rate for mice at a dose of 20 mg/kg) and low toxicity. NLD-22 had a favorable pharmacokinetic profile. High-resolution cryo-electron microscopy structural analysis confirmed NLD-22 bound to the hydrophobic pocket in VP1 to block viral infection. In general, NLD-22 was indicated to be a promising potential drug candidate for the treatment of HFMD.


  • Organizational Affiliation

    State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences and College of Pharmacy , Nankai University , Tianjin 300353 , China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein VP1297Enterovirus A71Mutation(s): 0 
EC: 3.4.22.29 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.4.22.28 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for B2ZUN0 (Human enterovirus 71)
Explore B2ZUN0 
Go to UniProtKB:  B2ZUN0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupB2ZUN0
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein VP2254Enterovirus A71Mutation(s): 0 
EC: 3.4.22.29 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.4.22.28 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for B2ZUN0 (Human enterovirus 71)
Explore B2ZUN0 
Go to UniProtKB:  B2ZUN0
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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupB2ZUN0
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein VP3242Enterovirus A71Mutation(s): 0 
EC: 3.4.22.29 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.4.22.28 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for B2ZUN0 (Human enterovirus 71)
Explore B2ZUN0 
Go to UniProtKB:  B2ZUN0
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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupB2ZUN0
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein VP469Enterovirus A71Mutation(s): 0 
EC: 3.4.22.29 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.4.22.28 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for B2ZUN0 (Human enterovirus 71)
Explore B2ZUN0 
Go to UniProtKB:  B2ZUN0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupB2ZUN0
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EQ9 (Subject of Investigation/LOI)
Query on EQ9

Download Ideal Coordinates CCD File 
E [auth A]1-(2-azanylpyridin-4-yl)-3-[5-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]pentyl]imidazolidin-2-one
C22 H26 N6 O3
HBOHAJJGWJLRSS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.26 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Ministry of Science and Technology (MoST, China)China2017YFC840300

Revision History  (Full details and data files)

  • Version 1.0: 2020-03-11
    Type: Initial release
  • Version 1.1: 2024-03-27
    Changes: Data collection, Database references, Derived calculations