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@ARTICLE{Gnther:456821,
author = {Günther, Sebastian and Reinke, Patrick Y. A. and
Fernández-García, Yaiza and Lieske, Julia and Lane, Thomas
J. and Ginn, Helen M. and Koua, Faisal H. M. and Ehrt,
Christiane and Ewert, Wiebke and Oberthuer, Dominik and
Yefanov, Oleksandr and Meier, Susanne and Lorenzen, Kristina
and Krichel, Boris and Kopicki, Janine-Denise and Gelisio,
Luca and Brehm, Wolfgang and Dunkel, Ilona and Seychell,
Brandon and Gieseler, Henry and Norton-Baker, Brenna and
Escudero-Pérez, Beatriz and Domaracky, Martin and Saouane,
Sofiane and Tolstikova, Alexandra and White, Thomas A. and
Hänle, Anna and Groessler, Michael and Fleckenstein, Holger
and Trost, Fabian and Galchenkova, Marina and Gevorkov,
Yaroslav and Li, Chufeng and Awel, Salah and Peck, Ariana
and Barthelmess, Miriam and Schluenzen, Frank and Lourdu
Xavier, Paulraj and Werner, Nadine and Andaleeb, Hina and
Ullah, Najeeb and Falke, Sven and Srinivasan, Vasundara and
França, Bruno Alves and Schwinzer, Martin and Brognaro,
Hévila and Rogers, Cromarte and Melo, Diogo and
Zaitseva-Doyle, Joanna J. and Knoska, Juraj and
Peña-Murillo, Gisel E. and Mashhour, Aida Rahmani and
Hennicke, Vincent and Fischer, Pontus and Hakanpää,
Johanna and Meyer, Jan and Gribbon, Philip and Ellinger,
Bernhard and Kuzikov, Maria and Wolf, Markus and Beccari,
Andrea R. and Bourenkov, Gleb and von Stetten, David and
Pompidor, Guillaume and Bento, Isabel and Panneerselvam,
Saravanan and Karpics, Ivars and Schneider, Thomas R. and
Garcia-Alai, Maria Marta and Niebling, Stephan and Guenther,
Christian and Schmidt, Christina and Schubert, Robin and
Han, Huijong and Boger, Juliane and Monteiro, Diana C. F.
and Zhang, Linlin and Sun, Xinyuanyuan and Pletzer-Zelgert,
Jonathan and Wollenhaupt, Jan and Feiler, Christian G. and
Weiss, Manfred S. and Schulz, Eike-Christian and Mehrabi,
Pedram and Karničar, Katarina and Usenik, Aleksandra and
Loboda, Jure and Tidow, Henning and Chari, Ashwin and
Hilgenfeld, Rolf and Uetrecht, Charlotte and Cox, Russell
and Zaliani, Andrea and Beck, Tobias and Rarey, Matthias and
Günther, Stephan and Turk, Dusan and Hinrichs, Winfried and
Chapman, Henry N. and Pearson, Arwen R. and Betzel,
Christian and Meents, Alke},
title = {{X}-ray screening identifies active site and allosteric
inhibitors of {SARS}-{C}o{V}-2 main protease},
journal = {Science / Science now},
volume = {372},
number = {6542},
issn = {1095-9203},
address = {Washington, DC},
publisher = {Assoc.},
reportid = {PUBDB-2021-01692},
pages = {642 - 646},
year = {2021},
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 (Mpro), 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 Mpro. In subsequent cell-based
viral reduction assays, one peptidomimetic and six
non-peptidic compounds showed antiviral activity at
non-toxic concentrations. We identified two allosteric
binding sites representing attractive targets for drug
development against SARS-CoV-2.},
cin = {CFEL-I / CFEL-TRSB / FS-PET-D / $FS_FS-SC$ / IT / EMBL / U
HH / FS-CSSB-GS / CFEL-ARD / Eur.XFEL / CSSB-LIV/DESY-CU /
CSSB-CF-SPC},
ddc = {320},
cid = {I:(DE-H253)CFEL-I-20161114 / I:(DE-H253)CFEL-TRSB-20161025
/ I:(DE-H253)FS-PET-D-20190712 /
$I:(DE-H253)FS_FS-SC-20201126$ / I:(DE-H253)IT-20120731 /
I:(DE-H253)EMBL-20120731 / $I:(DE-H253)U_HH-20120814$ /
I:(DE-H253)FS-CSSB-GS-20140815 /
I:(DE-H253)CFEL-ARD-20160914 /
$I:(DE-H253)Eur_XFEL-20120731$ /
$I:(DE-H253)CSSB-LIV_DESY-CU-20220525$ /
I:(DE-H253)CSSB-CF-SPC-20210520},
pnm = {633 - Life Sciences – Building Blocks of Life: Structure
and Function (POF4-633) / 6G3 - PETRA III (DESY) (POF4-6G3)
/ HIDSS-0002 - DASHH: Data Science in Hamburg - Helmholtz
Graduate School for the Structure of Matter
$(2019_IVF-HIDSS-0002)$ / AIM, DFG project
G:(GEPRIS)390715994 - EXC 2056: CUI: Advanced Imaging of
Matter (390715994) / EXSCALATE4CoV - EXaSCale smArt pLatform
Against paThogEns for Corona Virus (101003551) /
Ex-Net-0002-Phase2-3 - Advanced Imaging of Matter:
Structure, Dynamics and Control on the Atomic Scale - AIM
$(2018_Ex-Net-0002-Phase2-3)$ / DFG project
G:(GEPRIS)194651731 - EXC 1074: Hamburger Zentrum für
ultraschnelle Beobachtung (CUI): Struktur, Dynamik und
Kontrolle von Materie auf atomarer Skala (194651731)},
pid = {G:(DE-HGF)POF4-633 / G:(DE-HGF)POF4-6G3 /
$G:(DE-HGF)2019_IVF-HIDSS-0002$ / G:(GEPRIS)390715994 /
G:(EU-Grant)101003551 /
$G:(DE-HGF)2018_Ex-Net-0002-Phase2-3$ / G:(GEPRIS)194651731},
experiment = {EXP:(DE-H253)P-P11-20150101 / EXP:(DE-H253)P-P13-20150101 /
EXP:(DE-H253)P-P14-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33811162},
UT = {WOS:000649103500048},
doi = {10.1126/science.abf7945},
url = {https://bib-pubdb1.desy.de/record/456821},
}