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Journal Articles Molecular Informatics Year : 2023

A community effort in SARS‐CoV‐2 drug discovery

Johannes Schimunek (1) , Philipp Seidl , Katarina Elez , Tim Hempel , Tuan Le (2) , Frank Noé (3) , Simon Olsson , Lluís Raich (4) , Robin Winter , Hatice Gokcan (5) , Filipp Gusev , Evgeny Gutkin , Olexandr Isayev (5) , Maria Kurnikova , Chamali Narangoda , Roman Zubatyuk (6) , Ivan Bosko , Konstantin Furs , Anna Karpenko , Yury Kornoushenko , Mikita Shuldau , Artsemi Yushkevich , Mohammed Benabderrahmane (7) , Patrick Bousquet-Melou (8) , Ronan Bureau (7) , Beatrice Charton (9) , Bertrand Cirou , Gérard Gil , William Allen , Suman Sirimulla , Stanley Watowich , Nick Antonopoulos , Nikolaos Epitropakis , Agamemnon Krasoulis , Vassilis Pitsikalis , Stavros Theodorakis , Igor Kozlovskii , Anton Maliutin , Alexander Medvedev , Petr Popov , Mark Zaretckii , Hamid Eghbal-Zadeh , Christina Halmich , Sepp Hochreiter , Andreas Mayr , Peter Ruch , Michael Widrich , Francois Berenger , Ashutosh Kumar , Yoshihiro Yamanishi , Kam Zhang , Emmanuel Bengio , Yoshua Bengio , Moksh Jain , Maksym Korablyov , Cheng-Hao Liu , Marcous Gilles , Enrico Glaab , Kelly Barnsley , Suhasini Iyengar , Mary Jo Ondrechen , V. Joachim Haupt , Florian Kaiser , Michael Schroeder , Luisa Pugliese , Simone Albani , Christina Athanasiou , Andrea Beccari , Paolo Carloni , Giulia d'Arrigo , Eleonora Gianquinto , Jonas Goßen , Anton Hanke , Benjamin Joseph , Daria Kokh , Sandra Kovachka , Candida Manelfi , Goutam Mukherjee , Abraham Muñiz-Chicharro , Francesco Musiani , Ariane Nunes-Alves , Giulia Paiardi , Giulia Rossetti , S. Kashif Sadiq , Francesca Spyrakis , Carmine Talarico , Alexandros Tsengenes , Rebecca Wade , Conner Copeland , Jeremiah Gaiser , Daniel Olson , Amitava Roy , Vishwesh Venkatraman , Travis Wheeler , Haribabu Arthanari , Klara Blaschitz , Marco Cespugli , Vedat Durmaz , Konstantin Fackeldey , Patrick Fischer , Christoph Gorgulla , Christian Gruber , Karl Gruber , Michael Hetmann , Jamie Kinney , Krishna Das , Shreya Pandita , Amit Singh , Georg Steinkellner , Guilhem Tesseyre , Gerhard Wagner , Zi-Fu Wang , Ryan Yust , Dmitry Druzhilovskiy , Dmitry Filimonov , Pavel Pogodin , Vladimir Poroikov , Anastassia Rudik , Leonid Stolbov , Alexander Veselovsky , Maria de Rosa , Giada De Simone , Maria Gulotta , Jessica Lombino , Nedra Mekni , Ugo Perricone , Arturo Casini , Amanda Embree , D. Benjamin Gordon , David Lei , Katelin Pratt , Christopher Voigt , Kuang-Yu Chen (10) , Yves Jacob (11) , Tim Krischuns (10) , Pierre Lafaye (12) , Agnès Zettor (13) , M. Luis Rodríguez , Kris White , Daren Fearon , Frank von Delft , Martin Walsh , Dragos Horvath , Charles Brooks , Babak Falsafi , Bryan Ford , Adolfo García-Sastre , Sang Yup Lee , Nadia Naffakh (10) , Alexandre Varnek , Guenter Klambauer , Thomas Hermans
Philipp Seidl
  • Function : Author
Katarina Elez
  • Function : Author
Tim Hempel
  • Function : Author
Simon Olsson
  • Function : Author
Robin Winter
  • Function : Author
Filipp Gusev
  • Function : Author
Evgeny Gutkin
  • Function : Author
Maria Kurnikova
  • Function : Author
Chamali Narangoda
  • Function : Author
Ivan Bosko
  • Function : Author
Konstantin Furs
  • Function : Author
Anna Karpenko
  • Function : Author
Yury Kornoushenko
  • Function : Author
Mikita Shuldau
  • Function : Author
Artsemi Yushkevich
  • Function : Author
Patrick Bousquet-Melou
  • Function : Author
Bertrand Cirou
  • Function : Author
Gérard Gil
  • Function : Author
William Allen
  • Function : Author
Suman Sirimulla
  • Function : Author
Stanley Watowich
  • Function : Author
Nick Antonopoulos
  • Function : Author
Nikolaos Epitropakis
  • Function : Author
Agamemnon Krasoulis
  • Function : Author
Vassilis Pitsikalis
  • Function : Author
Stavros Theodorakis
  • Function : Author
Igor Kozlovskii
  • Function : Author
Anton Maliutin
  • Function : Author
Alexander Medvedev
  • Function : Author
Petr Popov
  • Function : Author
Mark Zaretckii
  • Function : Author
Hamid Eghbal-Zadeh
  • Function : Author
Christina Halmich
  • Function : Author
Sepp Hochreiter
  • Function : Author
Andreas Mayr
  • Function : Author
Peter Ruch
  • Function : Author
Michael Widrich
  • Function : Author
Francois Berenger
  • Function : Author
Ashutosh Kumar
  • Function : Author
Yoshihiro Yamanishi
  • Function : Author
Kam Zhang
  • Function : Author
Emmanuel Bengio
  • Function : Author
Yoshua Bengio
  • Function : Author
Moksh Jain
  • Function : Author
Maksym Korablyov
  • Function : Author
Cheng-Hao Liu
  • Function : Author
Marcous Gilles
  • Function : Author
Enrico Glaab
  • Function : Author
Kelly Barnsley
  • Function : Author
Suhasini Iyengar
  • Function : Author
Mary Jo Ondrechen
  • Function : Author
V. Joachim Haupt
  • Function : Author
Florian Kaiser
  • Function : Author
Michael Schroeder
  • Function : Author
Luisa Pugliese
  • Function : Author
Simone Albani
  • Function : Author
Christina Athanasiou
  • Function : Author
Andrea Beccari
  • Function : Author
Paolo Carloni
  • Function : Author
Giulia d'Arrigo
  • Function : Author
Eleonora Gianquinto
  • Function : Author
Jonas Goßen
  • Function : Author
Anton Hanke
  • Function : Author
Benjamin Joseph
  • Function : Author
Daria Kokh
  • Function : Author
Sandra Kovachka
  • Function : Author
Candida Manelfi
  • Function : Author
Goutam Mukherjee
  • Function : Author
Abraham Muñiz-Chicharro
  • Function : Author
Francesco Musiani
  • Function : Author
Ariane Nunes-Alves
  • Function : Author
Giulia Paiardi
  • Function : Author
Giulia Rossetti
  • Function : Author
S. Kashif Sadiq
  • Function : Author
Francesca Spyrakis
  • Function : Author
Carmine Talarico
  • Function : Author
Alexandros Tsengenes
  • Function : Author
Rebecca Wade
  • Function : Author
Conner Copeland
  • Function : Author
Jeremiah Gaiser
  • Function : Author
Daniel Olson
  • Function : Author
Amitava Roy
  • Function : Author
Vishwesh Venkatraman
  • Function : Author
Travis Wheeler
  • Function : Author
Haribabu Arthanari
  • Function : Author
Klara Blaschitz
  • Function : Author
Marco Cespugli
  • Function : Author
Vedat Durmaz
  • Function : Author
Konstantin Fackeldey
  • Function : Author
Patrick Fischer
  • Function : Author
Christoph Gorgulla
  • Function : Author
Christian Gruber
  • Function : Author
Karl Gruber
  • Function : Author
Michael Hetmann
  • Function : Author
Jamie Kinney
  • Function : Author
Krishna Das
  • Function : Author
Shreya Pandita
  • Function : Author
Amit Singh
  • Function : Author
Georg Steinkellner
  • Function : Author
Guilhem Tesseyre
  • Function : Author
Gerhard Wagner
  • Function : Author
Zi-Fu Wang
  • Function : Author
Ryan Yust
  • Function : Author
Dmitry Druzhilovskiy
  • Function : Author
Dmitry Filimonov
  • Function : Author
Pavel Pogodin
  • Function : Author
Vladimir Poroikov
  • Function : Author
Anastassia Rudik
  • Function : Author
Leonid Stolbov
  • Function : Author
Alexander Veselovsky
  • Function : Author
Maria de Rosa
  • Function : Author
Giada De Simone
  • Function : Author
Maria Gulotta
  • Function : Author
Jessica Lombino
  • Function : Author
Nedra Mekni
  • Function : Author
Ugo Perricone
  • Function : Author
Arturo Casini
  • Function : Author
Amanda Embree
  • Function : Author
D. Benjamin Gordon
  • Function : Author
David Lei
  • Function : Author
Katelin Pratt
  • Function : Author
Christopher Voigt
  • Function : Author
M. Luis Rodríguez
  • Function : Author
Kris White
  • Function : Author
Daren Fearon
  • Function : Author
Frank von Delft
  • Function : Author
Martin Walsh
  • Function : Author
Dragos Horvath
  • Function : Author
Charles Brooks
  • Function : Author
Babak Falsafi
  • Function : Author
Bryan Ford
  • Function : Author
Adolfo García-Sastre
  • Function : Author
Sang Yup Lee
  • Function : Author
Alexandre Varnek
  • Function : Author
Guenter Klambauer
  • Function : Author
Thomas Hermans
  • Function : Author

Abstract

The COVID‐19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small‐molecule drugs that are widely available, including in low‐ and middle‐income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the “Billion molecules against Covid‐19 challenge”, to identify small‐molecule inhibitors against SARS‐CoV‐2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find ‘consensus compounds’. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding‐, cleavage‐, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS‐CoV‐2 treatments.
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pasteur-04269641 , version 1 (03-11-2023)

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Attribution - NonCommercial

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Johannes Schimunek, Philipp Seidl, Katarina Elez, Tim Hempel, Tuan Le, et al.. A community effort in SARS‐CoV‐2 drug discovery. Molecular Informatics, In press, ⟨10.1002/minf.202300262⟩. ⟨pasteur-04269641⟩
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