%0 Electronic Article
%A Günther, Sebastian
%A Reinke, Patrick Y. A.
%A Fernández-García, Yaiza
%A Lieske, Julia
%A Lane, Thomas J.
%A Ginn, Helen M.
%A Koua, Faisal H. M.
%A Ehrt, Christiane
%A Ewert, Wiebke
%A Oberthuer, Dominik
%A Yefanov, Oleksandr
%A Meier, Susanne
%A Lorenzen, Kristina
%A Krichel, Boris
%A Kopicki, Janine-Denise
%A Gelisio, Luca
%A Brehm, Wolfgang
%A Dunkel, Ilona
%A Seychell, Brandon
%A Gieseler, Henry
%A Norton-Baker, Brenna
%A Escudero-Pérez, Beatriz
%A Domaracky, Martin
%A Saouane, Sofiane
%A Tolstikova, Alexandra
%A White, Thomas A.
%A Hänle, Anna
%A Groessler, Michael
%A Fleckenstein, Holger
%A Trost, Fabian
%A Galchenkova, Marina
%A Gevorkov, Yaroslav
%A Li, Chufeng
%A Awel, Salah
%A Peck, Ariana
%A Barthelmess, Miriam
%A Schluenzen, Frank
%A Lourdu Xavier, Paulraj
%A Werner, Nadine
%A Andaleeb, Hina
%A Ullah, Najeeb
%A Falke, Sven
%A Srinivasan, Vasundara
%A França, Bruno Alves
%A Schwinzer, Martin
%A Brognaro, Hévila
%A Rogers, Cromarte
%A Melo, Diogo
%A Zaitseva-Doyle, Joanna J.
%A Knoska, Juraj
%A Peña-Murillo, Gisel E.
%A Mashhour, Aida Rahmani
%A Hennicke, Vincent
%A Fischer, Pontus
%A Hakanpää, Johanna
%A Meyer, Jan
%A Gribbon, Philip
%A Ellinger, Bernhard
%A Kuzikov, Maria
%A Wolf, Markus
%A Beccari, Andrea R.
%A Bourenkov, Gleb
%A von Stetten, David
%A Pompidor, Guillaume
%A Bento, Isabel
%A Panneerselvam, Saravanan
%A Karpics, Ivars
%A Schneider, Thomas R.
%A Garcia-Alai, Maria Marta
%A Niebling, Stephan
%A Guenther, Christian
%A Schmidt, Christina
%A Schubert, Robin
%A Han, Huijong
%A Boger, Juliane
%A Monteiro, Diana C. F.
%A Zhang, Linlin
%A Sun, Xinyuanyuan
%A Pletzer-Zelgert, Jonathan
%A Wollenhaupt, Jan
%A Feiler, Christian G.
%A Weiss, Manfred S.
%A Schulz, Eike-Christian
%A Mehrabi, Pedram
%A Karničar, Katarina
%A Usenik, Aleksandra
%A Loboda, Jure
%A Tidow, Henning
%A Chari, Ashwin
%A Hilgenfeld, Rolf
%A Uetrecht, Charlotte
%A Cox, Russell
%A Zaliani, Andrea
%A Beck, Tobias
%A Rarey, Matthias
%A Günther, Stephan
%A Turk, Dusan
%A Hinrichs, Winfried
%A Chapman, Henry N.
%A Pearson, Arwen R.
%A Betzel, Christian
%A Meents, Alke
%T Inhibition of SARS-CoV-2 main protease by allosteric drug-binding
%M PUBDB-2022-04874
%D 2020
%X 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 two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for the virus replication and, thus, a potent drug target. 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 M<sup>pro</sup>. In subsequent cell-based viral reduction assays, one peptidomimetic and five 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.
%F PUB:(DE-HGF)25
%9 Preprint
%R 10.1101/2020.11.12.378422
%U https://bib-pubdb1.desy.de/record/482633