Computationally driven discovery of SARS-CoV-2 Mpro inhibitors: from design to experimental validation

Author:

El Khoury Léa1ORCID,Jing Zhifeng1ORCID,Cuzzolin Alberto2,Deplano Alessandro3,Loco Daniele1,Sattarov Boris1,Hédin Florent1ORCID,Wendeborn Sebastian4,Ho Chris1,El Ahdab Dina5ORCID,Jaffrelot Inizan Theo5,Sturlese Mattia6,Sosic Alice7,Volpiana Martina7,Lugato Angela7,Barone Marco7,Gatto Barbara7,Macchia Maria Ludovica7,Bellanda Massimo8,Battistutta Roberto8,Salata Cristiano9ORCID,Kondratov Ivan10,Iminov Rustam10,Khairulin Andrii10,Mykhalonok Yaroslav10,Pochepko Anton10,Chashka-Ratushnyi Volodymyr10,Kos Iaroslava10,Moro Stefano6ORCID,Montes Matthieu11,Ren Pengyu12,Ponder Jay W.1314ORCID,Lagardère Louis5,Piquemal Jean-Philip515ORCID,Sabbadin Davide1

Affiliation:

1. Qubit Pharmaceuticals, Incubateur Paris Biotech Santé, 24 Rue du Faubourg Saint Jacques, 75014 Paris, France

2. Chiesi Farmaceutici S.p.A, Nuovo Centro Ricerche, Largo Belloli 11a, 43122, Parma, Italy

3. Pharmacelera, Torre R, 4a planta, Despatx A05, Parc Cientific de Barcelona, Baldiri Reixac 8, 08028 Barcelona, Spain

4. University of Applied Sciences and Arts Northwestern Switzerland, School of LifeSciences, Hofackerstrasse 30, CH-4132 Muttenz, Switzerland

5. Sorbonne Université, Laboratoire de Chimie Théorique, UMR 7616 CNRS, 75005, Paris, France

6. Molecular Modeling Section, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, via F. Marzolo 5, 35131, Padova, Italy

7. Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131, Padova, Italy

8. Department of Chemistry, University of Padova, via Marzolo 1, 35131, Padova, Italy

9. Department of Molecular Medicine, University of Padua, via Gabelli 63, 35121, Padova, Italy

10. Enamine Ltd, 78 Chervonotkats'ka Str., Kyiv 02094, Ukraine

11. Laboratoire GBCM, EA7528, Conservatoire National des Arts et Métiers, Hesam Université, 2 Rue Conte, 75003 Paris, France

12. University of Texas at Austin, Department of Biomedical Engineering, TX 78712, USA

13. Department of Chemistry, Washington University in Saint Louis, MO 63130, USA

14. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, MO 63110, USA

15. Institut Universitaire de France, 75005, Paris, France

Abstract

The dominant binding mode of the QUB-00006-Int-07 main protease inhibitor during absolute binding free energy simulations.

Funder

H2020 European Research Council

Publisher

Royal Society of Chemistry (RSC)

Subject

General Chemistry

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