8HUX

Crystal structure of SARS-Cov-2 main protease P132H mutant in complex with S217622


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.74 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Structural basis for the inhibition of coronaviral main proteases by ensitrelvir.

Lin, C.Jiang, H.Li, W.Zeng, P.Zhou, X.Zhang, J.Li, J.

(2023) Structure 31: 1016-1024.e3

  • DOI: https://doi.org/10.1016/j.str.2023.06.010
  • Primary Citation of Related Structures:  
    8HUR, 8HUS, 8HUT, 8HUU, 8HUV, 8HUW, 8HUX

  • PubMed Abstract: 

    Main protease (M pro ) is a highly conserved cysteine protease that plays a vital role in the replication of coronaviruses, making it an attractive pan-coronaviral therapeutic target. Ensitrelvir (S-217622), developed by Shionogi, is the first orally active non-covalent, non-peptidic SARS-CoV-2 M pro inhibitor, which also displays antiviral efficacy against other human coronaviruses as well as SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs). Here, we report the crystal structures of the main proteases from SARS-CoV-2, SARS-CoV-2 VOC/VOIs, SARS-CoV, MERS-CoV, and HCoV-NL63 bound to the inhibitor S-217622. A detailed analysis of these structures illuminates key structural determinants essential for inhibition and elucidates the binding modes of the main proteases from different coronaviruses. Given the importance of the main protease for the treatment of coronaviral infection, structural insights obtained from this study could accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.


  • Organizational Affiliation

    College of Pharmaceutical Sciences, Gannan Medical University, Ganzhou 341000, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3C-like proteinase nsp5
A, B
299Severe acute respiratory syndrome coronavirus 2Mutation(s): 1 
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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
7YY (Subject of Investigation/LOI)
Query on 7YY

Download Ideal Coordinates CCD File 
C [auth A],
D [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
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.74 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.897α = 90
b = 99.379β = 108.441
c = 59.132γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHENIXphasing

Structure Validation

View Full Validation Report



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: 2023-06-21
    Type: Initial release
  • Version 1.1: 2024-02-07
    Changes: Data collection, Database references