A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics

Author:

Gossen Jonas123ORCID,Albani Simone123,Hanke Anton45,Joseph Benjamin P.123,Bergh Cathrine6,Kuzikov Maria7ORCID,Costanzi Elisa8,Manelfi Candida9,Storici Paola8,Gribbon Philip7,Beccari Andrea R.9,Talarico Carmine9,Spyrakis Francesca10ORCID,Lindahl Erik611,Zaliani Andrea7ORCID,Carloni Paolo11223ORCID,Wade Rebecca C.41314ORCID,Musiani Francesco15ORCID,Kokh Daria B.4ORCID,Rossetti Giulia121617ORCID

Affiliation:

1. Institute for Neuroscience and Medicine (INM-9), Forschungszentrum Jülich, Jülich, 52425, Germany

2. Institute for Advanced Simulations (IAS-5) “Computational biomedicine”, Forschungszentrum Jülich, Jülich, 52425, Germany

3. Faculty of Mathematics, Computer Science and Natural Sciences, RWTH Aachen, Aachen, 52062, Germany

4. Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloss-Wolfsbrunnenweg 35, Heidelberg, 69118, Germany

5. Institute of Pharmacy and Molecular Biotechnology (IPMB), Heidelberg University, Im Neuenheimer Feld 364, Heidelberg, 69120, Germany

6. Science for Life Laboratory & Swedish e-Science Research Center, Department of Applied Physics, KTH Royal Institute of Technology, Stockholm, 11428, Sweden

7. Department of Screening Port, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, Hamburg, 22525, Germany

8. Elettra-Sincrotrone Trieste S.C.p.A., SS 14-km 163,5 in AREA Science Park, Basovizza, Trieste, 34149, Italy

9. Dompé Farmaceutici SpA, Via Campo di Pile, L’Aquila, 67100, Italy

10. Department of Drug Science and Technology, University of Turin, via Giuria 9, Turin, 10125, Italy

11. Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, SE-106 91, Sweden

12. Institute for Molecular Neuroscience and Neuroimaging (INM-11), Forschungszentrum Jülich, Jülich, 52425, Germany

13. Zentrum für Molekulare Biologie der University Heidelberg, DKFZ-ZMBH Alliance, INF 282, Heidelberg, 69120, Germany

14. Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, INF 368, Heidelberg, 69120, Germany

15. Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy

16. Jülich Supercomputing Center (JSC), Forschungszentrum Jülich, Jülich, 52425, Germany

17. Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, RWTH Aachen University, Aachen, 44517, Germany

Funder

?EXaSCale smArt pLatform Against paThogEns for Corona Virus?Exscalate4CoV?

Publisher

American Chemical Society (ACS)

Subject

Pharmacology (medical),Pharmacology

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