8HEF

The Crystal structure of deuterated S-217622 (Ensitrelvir) bound to the main protease (3CLpro/Mpro) of SARS-CoV-2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.51 Å
  • R-Value Free: 0.170 
  • R-Value Work: 0.133 
  • R-Value Observed: 0.135 

Starting Model: experimental
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Ligand Structure Quality Assessment 


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Literature

Synthesis of deuterated S-217622 (Ensitrelvir) with antiviral activity against coronaviruses including SARS-CoV-2.

Yang, Y.Cao, L.Yan, M.Zhou, J.Yang, S.Xu, T.Huang, S.Li, K.Zhou, Q.Li, G.Zhu, Y.Cong, F.Zhang, H.Guo, D.Li, Y.Zhang, X.

(2023) Antiviral Res 213: 105586-105586

  • DOI: https://doi.org/10.1016/j.antiviral.2023.105586
  • Primary Citation of Related Structures:  
    8HEF

  • PubMed Abstract: 

    S-217622 (Ensitrelvir) is a reversible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CL pro ) inhibitor which obtained emergency regulatory approval in Japan for the treatment of SARS-CoV-2 infection on Nov 22, 2022. Herein, analogs of S-271622 with deuterium-for-hydrogen replacement were synthesized for comparison of the antiviral activities and pharmacokinetic (PK) profiles. Compared to the parent compound, C11-d2-S-217622 compound YY-278 retained in vitro activity against 3CL pro and SARS-CoV-2. X-ray crystal structural studies showed similar interactions of SARS-CoV-2 3CL pro with YY-278 and S-271622. The PK profiling revealed the relatively favorable bioavailability and plasma exposure of YY-278. In addition, YY-278, as well as S-217622, displayed broadly anti-coronaviral activities against 6 other coronaviruses that infect humans and animals. These results laid the foundation for further research on the therapeutic potential of YY-278 against COVID-19 and other coronaviral diseases.


  • Organizational Affiliation

    Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518000, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3C-like proteinase
A, B
301Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
EC: 3.4.22.69
UniProt
Find proteins for P0DTD1 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTD1 
Go to UniProtKB:  P0DTD1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DTD1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
7YY (Subject of Investigation/LOI)
Query on 7YY

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
6-[(6-chloranyl-2-methyl-indazol-5-yl)amino]-3-[(1-methyl-1,2,4-triazol-3-yl)methyl]-1-[[2,4,5-tris(fluoranyl)phenyl]methyl]-1,3,5-triazine-2,4-dione
C22 H17 Cl F3 N9 O2
QMPBBNUOBOFBFS-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
D [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.51 Å
  • R-Value Free: 0.170 
  • R-Value Work: 0.133 
  • R-Value Observed: 0.135 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.8α = 90
b = 99.06β = 108.8
c = 59.67γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
xia2data reduction
xia2data scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Not funded--

Revision History  (Full details and data files)

  • Version 1.0: 2023-04-19
    Type: Initial release
  • Version 1.1: 2023-08-30
    Changes: Data collection, Refinement description