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Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease

View ORCID ProfileSebastian Günther, View ORCID ProfilePatrick Y. A. Reinke, View ORCID ProfileYaiza Fernández-García, Julia Lieske, Thomas J. Lane, Helen Ginn, Faisal H. M. Koua, Christiane Ehrt, Wiebke Ewert, Dominik Oberthuer, Oleksandr Yefanov, Susanne Meier, Kristina Lorenzen, Boris Krichel, Janine-Denise Kopicki, Luca Gelisio, Wolfgang Brehm, Ilona Dunkel, Brandon Seychell, Henry Gieseler, Brenna Norton-Baker, Beatriz Escudero-Pérez, Martin Domaracky, Sofiane Saouane, Alexandra Tolstikova, Thomas A. White, Anna Hänle, Michael Groessler, Holger Fleckenstein, Fabian Trost, Marina Galchenkova, Yaroslav Gevorkov, Chufeng Li, Salah Awel, Ariana Peck, Miriam Barthelmess, Frank Schlünzen, P. Lourdu Xavier, Nadine Werner, Hina Andaleeb, Najeeb Ullah, Sven Falke, Vasundara Srinivasan, Bruno Alves Franca, Martin Schwinzer, Hévila Brognaro, Cromarte Rogers, Diogo Melo, Jo J. Zaitsev-Doyle, Juraj Knoska, Gisel E. Peña Murillo, Aida Rahmani Mashhour, Filip Guicking, Vincent Hennicke, Pontus Fischer, Johanna Hakanpää, Jan Meyer, Phil Gribbon, Bernhard Ellinger, Maria Kuzikov, Markus Wolf, Gleb Borenkov, David von Stetten, Guillaume Pompidor, Isabel Bento, Saravanan Panneerselvam, Ivars Karpics, Thomas R. Schneider, Maria Marta Garcia Alai, Stephan Niebling, Christian Günther, Christina Schmidt, Robin Schubert, Huijong Han, Juliane Boger, Diana C. F. Monteiro, Linlin Zhang, Xinyuanyuan Sun, Jonathan Pletzer-Zelgert, Jan Wollenhaupt, Christian G. Feiler, Manfred S. Weiss, Eike-Christian Schulz, Pedram Mehrabi, Katarina Karničar, Aleksandra Usenik, Jure Loboda, Henning Tidow, Ashwin Chari, View ORCID ProfileRolf Hilgenfeld, View ORCID ProfileCharlotte Uetrecht, Russell Cox, Andrea Zaliani, Tobias Beck, Matthias Rarey, Stephan Günther, View ORCID ProfileDusan Turk, View ORCID ProfileWinfried Hinrichs, Henry N. Chapman, Arwen R. Pearson, Christian Betzel, View ORCID ProfileAlke Meents
doi: https://doi.org/10.1101/2020.11.12.378422
Sebastian Günther
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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  • ORCID record for Sebastian Günther
  • For correspondence: sebastian.guenther@desy.de alke.meents@desy.de
Patrick Y. A. Reinke
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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  • ORCID record for Patrick Y. A. Reinke
Yaiza Fernández-García
2Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359 Hamburg, Germany
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  • ORCID record for Yaiza Fernández-García
Julia Lieske
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Thomas J. Lane
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Helen Ginn
3Diamond Light Source Ltd. Diamond House, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK
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Faisal H. M. Koua
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Christiane Ehrt
4Universität Hamburg, Center for Bioinformatics, Bundesstr. 43, 20146 Hamburg, Germany
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Wiebke Ewert
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Dominik Oberthuer
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Oleksandr Yefanov
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Susanne Meier
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
6Universität Hamburg, Institut für Nanostruktur-und Festkörperphysik, Luruper Chaussee 149, 22761 Hamburg, Germany
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Kristina Lorenzen
7European XFEL GmbH. Holzkoppel 4, 22869 Schenefeld, Germany
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Boris Krichel
8Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistraße 52, 20251 Hamburg, Germany
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Janine-Denise Kopicki
8Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistraße 52, 20251 Hamburg, Germany
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Luca Gelisio
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Wolfgang Brehm
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Ilona Dunkel
9Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany
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Brandon Seychell
10Universität Hamburg, Department of Chemistry, Institute of Physical Chemistry, Grindelallee 117, 20146 Hamburg, Germany
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Henry Gieseler
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
6Universität Hamburg, Institut für Nanostruktur-und Festkörperphysik, Luruper Chaussee 149, 22761 Hamburg, Germany
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Brenna Norton-Baker
11Max Planck Institute for the Structure and Dynamics of Matter, Luruper Chaussee 149, 22761 Hamburg, Germany
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Beatriz Escudero-Pérez
2Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359 Hamburg, Germany
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Martin Domaracky
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Sofiane Saouane
12Deutsches Elektronen Synchrotron (DESY), Photon Science, Notkestrasse 85, 22607, Hamburg, Germany
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Alexandra Tolstikova
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Thomas A. White
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Anna Hänle
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Michael Groessler
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Holger Fleckenstein
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Fabian Trost
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Marina Galchenkova
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Yaroslav Gevorkov
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
13Vision Systems, Hamburg University of Technology, 21071 Hamburg, Germany
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Chufeng Li
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Salah Awel
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Ariana Peck
14Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
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Miriam Barthelmess
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Frank Schlünzen
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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P. Lourdu Xavier
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
11Max Planck Institute for the Structure and Dynamics of Matter, Luruper Chaussee 149, 22761 Hamburg, Germany
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Nadine Werner
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Hina Andaleeb
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Najeeb Ullah
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Sven Falke
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Vasundara Srinivasan
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Bruno Alves Franca
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Martin Schwinzer
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Hévila Brognaro
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Cromarte Rogers
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
6Universität Hamburg, Institut für Nanostruktur-und Festkörperphysik, Luruper Chaussee 149, 22761 Hamburg, Germany
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Diogo Melo
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
6Universität Hamburg, Institut für Nanostruktur-und Festkörperphysik, Luruper Chaussee 149, 22761 Hamburg, Germany
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Jo J. Zaitsev-Doyle
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
6Universität Hamburg, Institut für Nanostruktur-und Festkörperphysik, Luruper Chaussee 149, 22761 Hamburg, Germany
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Juraj Knoska
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Gisel E. Peña Murillo
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Aida Rahmani Mashhour
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Filip Guicking
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Vincent Hennicke
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Pontus Fischer
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Johanna Hakanpää
12Deutsches Elektronen Synchrotron (DESY), Photon Science, Notkestrasse 85, 22607, Hamburg, Germany
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Jan Meyer
12Deutsches Elektronen Synchrotron (DESY), Photon Science, Notkestrasse 85, 22607, Hamburg, Germany
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Phil Gribbon
16Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany
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Bernhard Ellinger
16Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany
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Maria Kuzikov
16Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany
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Markus Wolf
16Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany
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Gleb Borenkov
17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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David von Stetten
17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Guillaume Pompidor
17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Isabel Bento
17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Ivars Karpics
17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Thomas R. Schneider
17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Maria Marta Garcia Alai
17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Stephan Niebling
17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Christian Günther
17EMBL Outstation Hamburg, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
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Christina Schmidt
7European XFEL GmbH. Holzkoppel 4, 22869 Schenefeld, Germany
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Robin Schubert
7European XFEL GmbH. Holzkoppel 4, 22869 Schenefeld, Germany
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Huijong Han
7European XFEL GmbH. Holzkoppel 4, 22869 Schenefeld, Germany
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Juliane Boger
18Institute of Molecular Medicine, University of Lübeck, 23562 Lübeck, Germany
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Diana C. F. Monteiro
19Hauptmann Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY, 14203, USA
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Linlin Zhang
18Institute of Molecular Medicine, University of Lübeck, 23562 Lübeck, Germany
20German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, University of Lübeck, 23562 Lübeck, Germany
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Xinyuanyuan Sun
18Institute of Molecular Medicine, University of Lübeck, 23562 Lübeck, Germany
20German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, University of Lübeck, 23562 Lübeck, Germany
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Jonathan Pletzer-Zelgert
4Universität Hamburg, Center for Bioinformatics, Bundesstr. 43, 20146 Hamburg, Germany
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Jan Wollenhaupt
21Helmholtz Zentrum Berlin, Macromolecular Crystallography, Albert-Einstein-Str. 15, 12489 Berlin, Germany
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Christian G. Feiler
21Helmholtz Zentrum Berlin, Macromolecular Crystallography, Albert-Einstein-Str. 15, 12489 Berlin, Germany
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Manfred S. Weiss
21Helmholtz Zentrum Berlin, Macromolecular Crystallography, Albert-Einstein-Str. 15, 12489 Berlin, Germany
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Eike-Christian Schulz
11Max Planck Institute for the Structure and Dynamics of Matter, Luruper Chaussee 149, 22761 Hamburg, Germany
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Pedram Mehrabi
11Max Planck Institute for the Structure and Dynamics of Matter, Luruper Chaussee 149, 22761 Hamburg, Germany
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Katarina Karničar
22Department of Biochemistry & Molecular & Structural Biology, Jozef Stefan Institute, Jamova 39, 1 000 Ljubljana, Slovenia
23Centre of excellence for Integrated Approaches in Chemistry and Biology of Proteins (CIPKEBIP), Jamova 39, 1 000 Ljubljana,Slovenia
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Aleksandra Usenik
22Department of Biochemistry & Molecular & Structural Biology, Jozef Stefan Institute, Jamova 39, 1 000 Ljubljana, Slovenia
23Centre of excellence for Integrated Approaches in Chemistry and Biology of Proteins (CIPKEBIP), Jamova 39, 1 000 Ljubljana,Slovenia
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Jure Loboda
22Department of Biochemistry & Molecular & Structural Biology, Jozef Stefan Institute, Jamova 39, 1 000 Ljubljana, Slovenia
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Henning Tidow
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
24Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
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Ashwin Chari
25Research Group for Structural Bichemistry and Mechanisms, Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany
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Rolf Hilgenfeld
18Institute of Molecular Medicine, University of Lübeck, 23562 Lübeck, Germany
20German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems Site, University of Lübeck, 23562 Lübeck, Germany
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Charlotte Uetrecht
8Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistraße 52, 20251 Hamburg, Germany
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Russell Cox
26nstitute for Organic Chemistry and BMWZ, Leibniz University of Hannover, Schneiderberg 38, 30167 Hannover, Germany
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Andrea Zaliani
16Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany
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Tobias Beck
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
10Universität Hamburg, Department of Chemistry, Institute of Physical Chemistry, Grindelallee 117, 20146 Hamburg, Germany
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Matthias Rarey
4Universität Hamburg, Center for Bioinformatics, Bundesstr. 43, 20146 Hamburg, Germany
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Stephan Günther
2Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359 Hamburg, Germany
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Dusan Turk
22Department of Biochemistry & Molecular & Structural Biology, Jozef Stefan Institute, Jamova 39, 1 000 Ljubljana, Slovenia
23Centre of excellence for Integrated Approaches in Chemistry and Biology of Proteins (CIPKEBIP), Jamova 39, 1 000 Ljubljana,Slovenia
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Winfried Hinrichs
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Henry N. Chapman
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
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Arwen R. Pearson
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
6Universität Hamburg, Institut für Nanostruktur-und Festkörperphysik, Luruper Chaussee 149, 22761 Hamburg, Germany
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Christian Betzel
5Hamburg Centre for Ultrafast Imaging (CUI), Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg, Germany
15Universität Hamburg, Department of Chemistry, Institute of Biochemistry and Molecular Biology and Laboratory for Structural Biology of Infection and Inflammation, c/o DESY, 22607 Hamburg, Germany
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Alke Meents
1Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany
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  • For correspondence: sebastian.guenther@desy.de alke.meents@desy.de
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Summary

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of repurposing drug libraries1 containing 5953 individual compounds against the SARS-CoV-2 main protease (Mpro), which is a potent drug target as it is essential for the virus replication2. 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 binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. Interestingly, two compounds bind outside the active site to the native dimer interface in close proximity to the S1 binding pocket. Another compound binds in a cleft between the catalytic and dimerization domain of Mpro. Neither binding site is related to the enzymatic active site and both represent attractive targets for drug development against SARS-CoV-2. This X-ray screening approach thus has the potential to help deliver an approved drug on an accelerated time-scale for this and future pandemics3.

Competing Interest Statement

The authors have declared no competing interest.

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Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease
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Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease
Sebastian Günther, Patrick Y. A. Reinke, Yaiza Fernández-García, Julia Lieske, Thomas J. Lane, Helen Ginn, Faisal H. M. Koua, Christiane Ehrt, Wiebke Ewert, Dominik Oberthuer, Oleksandr Yefanov, Susanne Meier, Kristina Lorenzen, Boris Krichel, Janine-Denise Kopicki, Luca Gelisio, Wolfgang Brehm, Ilona Dunkel, Brandon Seychell, Henry Gieseler, Brenna Norton-Baker, Beatriz Escudero-Pérez, Martin Domaracky, Sofiane Saouane, Alexandra Tolstikova, Thomas A. White, Anna Hänle, Michael Groessler, Holger Fleckenstein, Fabian Trost, Marina Galchenkova, Yaroslav Gevorkov, Chufeng Li, Salah Awel, Ariana Peck, Miriam Barthelmess, Frank Schlünzen, P. Lourdu Xavier, Nadine Werner, Hina Andaleeb, Najeeb Ullah, Sven Falke, Vasundara Srinivasan, Bruno Alves Franca, Martin Schwinzer, Hévila Brognaro, Cromarte Rogers, Diogo Melo, Jo J. Zaitsev-Doyle, Juraj Knoska, Gisel E. Peña Murillo, Aida Rahmani Mashhour, Filip Guicking, Vincent Hennicke, Pontus Fischer, Johanna Hakanpää, Jan Meyer, Phil Gribbon, Bernhard Ellinger, Maria Kuzikov, Markus Wolf, Gleb Borenkov, David von Stetten, Guillaume Pompidor, Isabel Bento, Saravanan Panneerselvam, Ivars Karpics, Thomas R. Schneider, Maria Marta Garcia Alai, Stephan Niebling, Christian Günther, Christina Schmidt, Robin Schubert, Huijong Han, Juliane Boger, Diana C. F. Monteiro, Linlin Zhang, Xinyuanyuan Sun, Jonathan Pletzer-Zelgert, Jan Wollenhaupt, Christian G. Feiler, Manfred S. Weiss, Eike-Christian Schulz, Pedram Mehrabi, Katarina Karničar, Aleksandra Usenik, Jure Loboda, Henning Tidow, Ashwin Chari, Rolf Hilgenfeld, Charlotte Uetrecht, Russell Cox, Andrea Zaliani, Tobias Beck, Matthias Rarey, Stephan Günther, Dusan Turk, Winfried Hinrichs, Henry N. Chapman, Arwen R. Pearson, Christian Betzel, Alke Meents
bioRxiv 2020.11.12.378422; doi: https://doi.org/10.1101/2020.11.12.378422
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Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease
Sebastian Günther, Patrick Y. A. Reinke, Yaiza Fernández-García, Julia Lieske, Thomas J. Lane, Helen Ginn, Faisal H. M. Koua, Christiane Ehrt, Wiebke Ewert, Dominik Oberthuer, Oleksandr Yefanov, Susanne Meier, Kristina Lorenzen, Boris Krichel, Janine-Denise Kopicki, Luca Gelisio, Wolfgang Brehm, Ilona Dunkel, Brandon Seychell, Henry Gieseler, Brenna Norton-Baker, Beatriz Escudero-Pérez, Martin Domaracky, Sofiane Saouane, Alexandra Tolstikova, Thomas A. White, Anna Hänle, Michael Groessler, Holger Fleckenstein, Fabian Trost, Marina Galchenkova, Yaroslav Gevorkov, Chufeng Li, Salah Awel, Ariana Peck, Miriam Barthelmess, Frank Schlünzen, P. Lourdu Xavier, Nadine Werner, Hina Andaleeb, Najeeb Ullah, Sven Falke, Vasundara Srinivasan, Bruno Alves Franca, Martin Schwinzer, Hévila Brognaro, Cromarte Rogers, Diogo Melo, Jo J. Zaitsev-Doyle, Juraj Knoska, Gisel E. Peña Murillo, Aida Rahmani Mashhour, Filip Guicking, Vincent Hennicke, Pontus Fischer, Johanna Hakanpää, Jan Meyer, Phil Gribbon, Bernhard Ellinger, Maria Kuzikov, Markus Wolf, Gleb Borenkov, David von Stetten, Guillaume Pompidor, Isabel Bento, Saravanan Panneerselvam, Ivars Karpics, Thomas R. Schneider, Maria Marta Garcia Alai, Stephan Niebling, Christian Günther, Christina Schmidt, Robin Schubert, Huijong Han, Juliane Boger, Diana C. F. Monteiro, Linlin Zhang, Xinyuanyuan Sun, Jonathan Pletzer-Zelgert, Jan Wollenhaupt, Christian G. Feiler, Manfred S. Weiss, Eike-Christian Schulz, Pedram Mehrabi, Katarina Karničar, Aleksandra Usenik, Jure Loboda, Henning Tidow, Ashwin Chari, Rolf Hilgenfeld, Charlotte Uetrecht, Russell Cox, Andrea Zaliani, Tobias Beck, Matthias Rarey, Stephan Günther, Dusan Turk, Winfried Hinrichs, Henry N. Chapman, Arwen R. Pearson, Christian Betzel, Alke Meents
bioRxiv 2020.11.12.378422; doi: https://doi.org/10.1101/2020.11.12.378422

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