RCSB PDB - 7AF0: Structure of SARS-CoV-2 Main Protease bound to Ipidacrine.

 7AF0

Structure of SARS-CoV-2 Main Protease bound to Ipidacrine.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 

Starting Model: experimental
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Ligand Structure Quality Assessment 

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Literature

X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease.

Gunther, S.Reinke, P.Y.A.Fernandez-Garcia, Y.Lieske, J.Lane, T.J.Ginn, H.M.Koua, F.H.M.Ehrt, C.Ewert, W.Oberthuer, D.Yefanov, O.Meier, S.Lorenzen, K.Krichel, B.Kopicki, J.D.Gelisio, L.Brehm, W.Dunkel, I.Seychell, B.Gieseler, H.Norton-Baker, B.Escudero-Perez, B.Domaracky, M.Saouane, S.Tolstikova, A.White, T.A.Hanle, A.Groessler, M.Fleckenstein, H.Trost, F.Galchenkova, M.Gevorkov, Y.Li, C.Awel, S.Peck, A.Barthelmess, M.Schlunzen, F.Lourdu Xavier, P.Werner, N.Andaleeb, H.Ullah, N.Falke, S.Srinivasan, V.Franca, B.A.Schwinzer, M.Brognaro, H.Rogers, C.Melo, D.Zaitseva-Doyle, J.J.Knoska, J.Pena-Murillo, G.E.Mashhour, A.R.Hennicke, V.Fischer, P.Hakanpaa, J.Meyer, J.Gribbon, P.Ellinger, B.Kuzikov, M.Wolf, M.Beccari, A.R.Bourenkov, G.von Stetten, D.Pompidor, G.Bento, I.Panneerselvam, S.Karpics, I.Schneider, T.R.Garcia-Alai, M.M.Niebling, S.Gunther, C.Schmidt, C.Schubert, R.Han, H.Boger, J.Monteiro, D.C.F.Zhang, L.Sun, X.Pletzer-Zelgert, J.Wollenhaupt, J.Feiler, C.G.Weiss, M.S.Schulz, E.C.Mehrabi, P.Karnicar, K.Usenik, A.Loboda, J.Tidow, H.Chari, A.Hilgenfeld, R.Uetrecht, C.Cox, R.Zaliani, A.Beck, T.Rarey, M.Gunther, S.Turk, D.Hinrichs, W.Chapman, H.N.Pearson, A.R.Betzel, C.Meents, A.

(2021) Science 372: 642-646

  • DOI: https://doi.org/10.1126/science.abf7945
  • Primary Citation of Related Structures:  
    6YNQ, 6YVF, 7A1U, 7ABU, 7ADW, 7AF0, 7AGA, 7AHA, 7AK4, 7AKU, 7AMJ, 7ANS, 7AOL, 7AP6, 7APH, 7AQE, 7AQI, 7AQJ, 7AR5, 7AR6, 7ARF, 7AVD, 7AWR, 7AWS, 7AWU, 7AWW, 7AX6, 7AXM, 7AXO, 7AY7, 7B83, 7NEV

  • PubMed Abstract: 

    The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput x-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (M pro ), which is essential for viral replication. In contrast to commonly applied x-ray fragment screening experiments with molecules of low complexity, our screen tested already-approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to M pro In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.


  • Organizational Affiliation

    Center for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607 Hamburg, Germany. sebastian.guenther@desy.de alke.meents@desy.de.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3C-like proteinase306Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
Gene Names: rep1a-1b
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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.753α = 90
b = 52.96β = 102.9
c = 44.842γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
REFMACphasing

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted R9WClick on this verticalbar to view details

Entry History & Funding Information

Revision History  (Full details and data files)

  • Version 1.0: 2020-12-02
    Type: Initial release
  • Version 1.1: 2020-12-09
    Changes: Database references
  • Version 1.2: 2021-04-14
    Changes: Database references, Source and taxonomy, Structure summary
  • Version 1.3: 2021-05-19
    Changes: Database references
  • Version 1.4: 2024-01-31
    Changes: Data collection, Database references, Refinement description