A community effort in SARS-CoV-2 drug discovery

Johannes Schimunek; Philipp Seidl; Katarina Elez; Tim Hempel; Tuan Le; Frank Noé; Simon Olsson; Lluís Raich; Robin Winter; Hatice Gokcan; Filipp Gusev; Evgeny M. Gutkin; Olexandr Isayev; Maria G. Kurnikova; Chamali H. Narangoda; Roman Zubatyuk; Ivan P. Bosko; Konstantin V. Furs; Anna D. Karpenko; Yury V. Kornoushenko; Mikita Shuldau; Artsemi Yushkevich; Mohammed B. Benabderrahmane; Patrick Bousquet-Melou; Ronan Bureau; Beatrice Charton; Bertrand C. Cirou; Gérard Gil; William J. Allen; Suman Sirimulla; Stanley Watowich; Nick Antonopoulos; Nikolaos Epitropakis; Agamemnon Krasoulis; Vassilis Itsikalis; 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 Y.J. Zhang; Emmanuel Bengio; Yoshua Bengio; Moksh J. Jain; Maksym Korablyov; Cheng Hao Liu; Gilles Marcou; Enrico Glaab; Kelly Barnsley; Suhasini M. 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 P. Joseph; Daria B. 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 C. Wade; Conner Copeland; Jeremiah Gaiser; Daniel R. Olson; Amitava Roy; Vishwesh Venkatraman; Travis J. Wheeler; Haribabu Arthanari; Klara Blaschitz; Marco Cespugli; Vedat Durmaz; Konstantin Fackeldey; Patrick D. Fischer; Christoph Gorgulla; Christian Gruber; Karl Gruber; Michael Hetmann; Jamie E. Kinney; Krishna M. Padmanabha Das; Shreya Pandita; Amit Singh; Georg Steinkellner; Guilhem Tesseyre; Gerhard Wagner; Zi Fu Wang; Ryan J. Yust; Dmitry S. Druzhilovskiy; Dmitry A. Filimonov; Pavel V. Pogodin; Vladimir Poroikov; Anastassia V. Rudik; Leonid A. Stolbov; Alexander V. Veselovsky; Maria De Rosa; Giada De Simone; Maria R. Gulotta; Jessica Lombino; Nedra Mekni; Ugo Perricone; Arturo Casini; Amanda Embree; D. Benjamin Gordon; David Lei; Katelin Pratt; Christopher A. Voigt; Kuang Yu Chen; Yves Jacob; Tim Krischuns; Pierre Lafaye; Agnès Zettor; M. Luis Rodríguez; Kris M. White; Daren Fearon; Frank Von Delft; Martin A. Walsh; Dragos Horvath; Charles L. Brooks; Babak Falsafi; Bryan Ford; Adolfo García-Sastre; Sang Yup Lee; Nadia Naffakh; Alexandre Varnek; Günter Klambauer; Thomas M. Hermans

doi:10.1002/minf.202300262

A community effort in SARS-CoV-2 drug discovery

Johannes Schimunek, Philipp Seidl, Katarina Elez, Tim Hempel, Tuan Le, Frank Noé, Simon Olsson, Lluís Raich, Robin Winter, Hatice Gokcan, Filipp Gusev, Evgeny M. Gutkin, Olexandr Isayev, Maria G. Kurnikova, Chamali H. Narangoda, Roman Zubatyuk, Ivan P. Bosko, Konstantin V. Furs, Anna D. Karpenko, Yury V. KornoushenkoMikita Shuldau, Artsemi Yushkevich, Mohammed B. Benabderrahmane, Patrick Bousquet-Melou, Ronan Bureau, Beatrice Charton, Bertrand C. Cirou, Gérard Gil, William J. Allen, Suman Sirimulla, Stanley Watowich, Nick Antonopoulos, Nikolaos Epitropakis, Agamemnon Krasoulis, Vassilis Itsikalis, 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 Y.J. Zhang, Emmanuel Bengio, Yoshua Bengio, Moksh J. Jain, Maksym Korablyov, Cheng Hao Liu, Gilles Marcou, Enrico Glaab, Kelly Barnsley, Suhasini M. 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 P. Joseph, Daria B. 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 C. Wade, Conner Copeland, Jeremiah Gaiser, Daniel R. Olson, Amitava Roy, Vishwesh Venkatraman, Travis J. Wheeler, Haribabu Arthanari, Klara Blaschitz, Marco Cespugli, Vedat Durmaz, Konstantin Fackeldey, Patrick D. Fischer, Christoph Gorgulla, Christian Gruber, Karl Gruber, Michael Hetmann, Jamie E. Kinney, Krishna M. Padmanabha Das, Shreya Pandita, Amit Singh, Georg Steinkellner, Guilhem Tesseyre, Gerhard Wagner, Zi Fu Wang, Ryan J. Yust, Dmitry S. Druzhilovskiy, Dmitry A. Filimonov, Pavel V. Pogodin, Vladimir Poroikov, Anastassia V. Rudik, Leonid A. Stolbov, Alexander V. Veselovsky, Maria De Rosa, Giada De Simone, Maria R. Gulotta, Jessica Lombino, Nedra Mekni, Ugo Perricone, Arturo Casini, Amanda Embree, D. Benjamin Gordon, David Lei, Katelin Pratt, Christopher A. Voigt, Kuang Yu Chen, Yves Jacob, Tim Krischuns, Pierre Lafaye, Agnès Zettor, M. Luis Rodríguez, Kris M. White, Daren Fearon, Frank Von Delft, Martin A. Walsh, Dragos Horvath, Charles L. Brooks, Babak Falsafi, Bryan Ford, Adolfo García-Sastre, Sang Yup Lee, Nadia Naffakh, Alexandre Varnek, Günter Klambauer, Thomas M. Hermans

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	e202300262
Journal	Molecular Informatics
Volume	43
Issue number	1
DOIs	https://doi.org/10.1002/minf.202300262
State	Published - Jan 2024

Keywords

COVID-19
SARS-CoV-2
drug discovery
machine learning

ASJC Scopus subject areas

Structural Biology
Molecular Medicine
Drug Discovery
Computer Science Applications
Organic Chemistry

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10.1002/minf.202300262

Cite this

Schimunek, J., Seidl, P., Elez, K., Hempel, T., Le, T., Noé, F., Olsson, S., Raich, L., Winter, R., Gokcan, H., Gusev, F., Gutkin, E. M., Isayev, O., Kurnikova, M. G., Narangoda, C. H., Zubatyuk, R., Bosko, I. P., Furs, K. V., Karpenko, A. D., ... Hermans, T. M. (2024). A community effort in SARS-CoV-2 drug discovery. Molecular Informatics, 43(1), Article e202300262. https://doi.org/10.1002/minf.202300262

Schimunek, J, Seidl, P, Elez, K, Hempel, T, Le, T, Noé, F, Olsson, S, Raich, L, Winter, R, Gokcan, H, Gusev, F, Gutkin, EM, Isayev, O, Kurnikova, MG, Narangoda, CH, Zubatyuk, R, Bosko, IP, Furs, KV, Karpenko, AD, Kornoushenko, YV, Shuldau, M, Yushkevich, A, Benabderrahmane, MB, Bousquet-Melou, P, Bureau, R, Charton, B, Cirou, BC, Gil, G, Allen, WJ, Sirimulla, S, Watowich, S, Antonopoulos, N, Epitropakis, N, Krasoulis, A, Itsikalis, V, Theodorakis, S, Kozlovskii, I, Maliutin, A, Medvedev, A, Popov, P, Zaretckii, M, Eghbal-Zadeh, H, Halmich, C, Hochreiter, S, Mayr, A, Ruch, P, Widrich, M, Berenger, F, Kumar, A, Yamanishi, Y, Zhang, KYJ, Bengio, E, Bengio, Y, Jain, MJ, Korablyov, M, Liu, CH, Marcou, G, Glaab, E, Barnsley, K, Iyengar, SM, Ondrechen, MJ, Haupt, VJ, Kaiser, F, Schroeder, M, Pugliese, L, Albani, S, Athanasiou, C, Beccari, A, Carloni, P, D'Arrigo, G, Gianquinto, E, Goßen, J, Hanke, A, Joseph, BP, Kokh, DB, Kovachka, S, Manelfi, C, Mukherjee, G, Muñiz-Chicharro, A, Musiani, F, Nunes-Alves, A, Paiardi, G, Rossetti, G, Sadiq, SK, Spyrakis, F, Talarico, C, Tsengenes, A, Wade, RC, Copeland, C, Gaiser, J, Olson, DR, Roy, A, Venkatraman, V, Wheeler, TJ, Arthanari, H, Blaschitz, K, Cespugli, M, Durmaz, V, Fackeldey, K, Fischer, PD, Gorgulla, C, Gruber, C, Gruber, K, Hetmann, M, Kinney, JE, Padmanabha Das, KM, Pandita, S, Singh, A, Steinkellner, G, Tesseyre, G, Wagner, G, Wang, ZF, Yust, RJ, Druzhilovskiy, DS, Filimonov, DA, Pogodin, PV, Poroikov, V, Rudik, AV, Stolbov, LA, Veselovsky, AV, De Rosa, M, De Simone, G, Gulotta, MR, Lombino, J, Mekni, N, Perricone, U, Casini, A, Embree, A, Gordon, DB, Lei, D, Pratt, K, Voigt, CA, Chen, KY, Jacob, Y, Krischuns, T, Lafaye, P, Zettor, A, Rodríguez, ML, White, KM, Fearon, D, Von Delft, F, Walsh, MA, Horvath, D, Brooks, CL, Falsafi, B, Ford, B, García-Sastre, A, Yup Lee, S, Naffakh, N, Varnek, A, Klambauer, G & Hermans, TM 2024, 'A community effort in SARS-CoV-2 drug discovery', Molecular Informatics, vol. 43, no. 1, e202300262. https://doi.org/10.1002/minf.202300262

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title = "A community effort in SARS-CoV-2 drug discovery",

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 {\textquoteleft}consensus compounds{\textquoteright}. 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.",

keywords = "COVID-19, SARS-CoV-2, drug discovery, machine learning",

author = "Johannes Schimunek and Philipp Seidl and Katarina Elez and Tim Hempel and Tuan Le and Frank No{\'e} and Simon Olsson and Llu{\'i}s Raich and Robin Winter and Hatice Gokcan and Filipp Gusev and Gutkin, {Evgeny M.} and Olexandr Isayev and Kurnikova, {Maria G.} and Narangoda, {Chamali H.} and Roman Zubatyuk and Bosko, {Ivan P.} and Furs, {Konstantin V.} and Karpenko, {Anna D.} and Kornoushenko, {Yury V.} and Mikita Shuldau and Artsemi Yushkevich and Benabderrahmane, {Mohammed B.} and Patrick Bousquet-Melou and Ronan Bureau and Beatrice Charton and Cirou, {Bertrand C.} and G{\'e}rard Gil and Allen, {William J.} and Suman Sirimulla and Stanley Watowich and Nick Antonopoulos and Nikolaos Epitropakis and Agamemnon Krasoulis and Vassilis Itsikalis and Stavros Theodorakis and Igor Kozlovskii and Anton Maliutin and Alexander Medvedev and Petr Popov and Mark Zaretckii and Hamid Eghbal-Zadeh and Christina Halmich and Sepp Hochreiter and Andreas Mayr and Peter Ruch and Michael Widrich and Francois Berenger and Ashutosh Kumar and Yoshihiro Yamanishi and Zhang, {Kam Y.J.} and Emmanuel Bengio and Yoshua Bengio and Jain, {Moksh J.} and Maksym Korablyov and Liu, {Cheng Hao} and Gilles Marcou and Enrico Glaab and Kelly Barnsley and Iyengar, {Suhasini M.} and Ondrechen, {Mary Jo} and Haupt, {V. Joachim} and Florian Kaiser and Michael Schroeder and Luisa Pugliese and Simone Albani and Christina Athanasiou and Andrea Beccari and Paolo Carloni and Giulia D'Arrigo and Eleonora Gianquinto and Jonas Go{\ss}en and Anton Hanke and Joseph, {Benjamin P.} and Kokh, {Daria B.} and Sandra Kovachka and Candida Manelfi and Goutam Mukherjee and Abraham Mu{\~n}iz-Chicharro and Francesco Musiani and Ariane Nunes-Alves and Giulia Paiardi and Giulia Rossetti and Sadiq, {S. Kashif} and Francesca Spyrakis and Carmine Talarico and Alexandros Tsengenes and Wade, {Rebecca C.} and Conner Copeland and Jeremiah Gaiser and Olson, {Daniel R.} and Amitava Roy and Vishwesh Venkatraman and Wheeler, {Travis J.} and Haribabu Arthanari and Klara Blaschitz and Marco Cespugli and Vedat Durmaz and Konstantin Fackeldey and Fischer, {Patrick D.} and Christoph Gorgulla and Christian Gruber and Karl Gruber and Michael Hetmann and Kinney, {Jamie E.} and {Padmanabha Das}, {Krishna M.} and Shreya Pandita and Amit Singh and Georg Steinkellner and Guilhem Tesseyre and Gerhard Wagner and Wang, {Zi Fu} and Yust, {Ryan J.} and Druzhilovskiy, {Dmitry S.} and Filimonov, {Dmitry A.} and Pogodin, {Pavel V.} and Vladimir Poroikov and Rudik, {Anastassia V.} and Stolbov, {Leonid A.} and Veselovsky, {Alexander V.} and {De Rosa}, Maria and {De Simone}, Giada and Gulotta, {Maria R.} and Jessica Lombino and Nedra Mekni and Ugo Perricone and Arturo Casini and Amanda Embree and Gordon, {D. Benjamin} and David Lei and Katelin Pratt and Voigt, {Christopher A.} and Chen, {Kuang Yu} and Yves Jacob and Tim Krischuns and Pierre Lafaye and Agn{\`e}s Zettor and Rodr{\'i}guez, {M. Luis} and White, {Kris M.} and Daren Fearon and {Von Delft}, Frank and Walsh, {Martin A.} and Dragos Horvath and Brooks, {Charles L.} and Babak Falsafi and Bryan Ford and Adolfo Garc{\'i}a-Sastre and {Yup Lee}, Sang and Nadia Naffakh and Alexandre Varnek and G{\"u}nter Klambauer and Hermans, {Thomas M.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Molecular Informatics published by Wiley-VCH GmbH.",

year = "2024",

month = jan,

doi = "10.1002/minf.202300262",

language = "English (US)",

volume = "43",

journal = "Molecular Informatics",

issn = "1868-1743",

publisher = "Wiley - VCH Verlag GmbH & CO. KGaA",

number = "1",

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TY - JOUR

T1 - A community effort in SARS-CoV-2 drug discovery

AU - Schimunek, Johannes

AU - Seidl, Philipp

AU - Elez, Katarina

AU - Hempel, Tim

AU - Le, Tuan

AU - Noé, Frank

AU - Olsson, Simon

AU - Raich, Lluís

AU - Winter, Robin

AU - Gokcan, Hatice

AU - Gusev, Filipp

AU - Gutkin, Evgeny M.

AU - Isayev, Olexandr

AU - Kurnikova, Maria G.

AU - Narangoda, Chamali H.

AU - Zubatyuk, Roman

AU - Bosko, Ivan P.

AU - Furs, Konstantin V.

AU - Karpenko, Anna D.

AU - Kornoushenko, Yury V.

AU - Shuldau, Mikita

AU - Yushkevich, Artsemi

AU - Benabderrahmane, Mohammed B.

AU - Bousquet-Melou, Patrick

AU - Bureau, Ronan

AU - Charton, Beatrice

AU - Cirou, Bertrand C.

AU - Gil, Gérard

AU - Allen, William J.

AU - Sirimulla, Suman

AU - Watowich, Stanley

AU - Antonopoulos, Nick

AU - Epitropakis, Nikolaos

AU - Krasoulis, Agamemnon

AU - Itsikalis, Vassilis

AU - Theodorakis, Stavros

AU - Kozlovskii, Igor

AU - Maliutin, Anton

AU - Medvedev, Alexander

AU - Popov, Petr

AU - Zaretckii, Mark

AU - Eghbal-Zadeh, Hamid

AU - Halmich, Christina

AU - Hochreiter, Sepp

AU - Mayr, Andreas

AU - Ruch, Peter

AU - Widrich, Michael

AU - Berenger, Francois

AU - Kumar, Ashutosh

AU - Yamanishi, Yoshihiro

AU - Zhang, Kam Y.J.

AU - Bengio, Emmanuel

AU - Bengio, Yoshua

AU - Jain, Moksh J.

AU - Korablyov, Maksym

AU - Liu, Cheng Hao

AU - Marcou, Gilles

AU - Glaab, Enrico

AU - Barnsley, Kelly

AU - Iyengar, Suhasini M.

AU - Ondrechen, Mary Jo

AU - Haupt, V. Joachim

AU - Kaiser, Florian

AU - Schroeder, Michael

AU - Pugliese, Luisa

AU - Albani, Simone

AU - Athanasiou, Christina

AU - Beccari, Andrea

AU - Carloni, Paolo

AU - D'Arrigo, Giulia

AU - Gianquinto, Eleonora

AU - Goßen, Jonas

AU - Hanke, Anton

AU - Joseph, Benjamin P.

AU - Kokh, Daria B.

AU - Kovachka, Sandra

AU - Manelfi, Candida

AU - Mukherjee, Goutam

AU - Muñiz-Chicharro, Abraham

AU - Musiani, Francesco

AU - Nunes-Alves, Ariane

AU - Paiardi, Giulia

AU - Rossetti, Giulia

AU - Sadiq, S. Kashif

AU - Spyrakis, Francesca

AU - Talarico, Carmine

AU - Tsengenes, Alexandros

AU - Wade, Rebecca C.

AU - Copeland, Conner

AU - Gaiser, Jeremiah

AU - Olson, Daniel R.

AU - Roy, Amitava

AU - Venkatraman, Vishwesh

AU - Wheeler, Travis J.

AU - Arthanari, Haribabu

AU - Blaschitz, Klara

AU - Cespugli, Marco

AU - Durmaz, Vedat

AU - Fackeldey, Konstantin

AU - Fischer, Patrick D.

AU - Gorgulla, Christoph

AU - Gruber, Christian

AU - Gruber, Karl

AU - Hetmann, Michael

AU - Kinney, Jamie E.

AU - Padmanabha Das, Krishna M.

AU - Pandita, Shreya

AU - Singh, Amit

AU - Steinkellner, Georg

AU - Tesseyre, Guilhem

AU - Wagner, Gerhard

AU - Wang, Zi Fu

AU - Yust, Ryan J.

AU - Druzhilovskiy, Dmitry S.

AU - Filimonov, Dmitry A.

AU - Pogodin, Pavel V.

AU - Poroikov, Vladimir

AU - Rudik, Anastassia V.

AU - Stolbov, Leonid A.

AU - Veselovsky, Alexander V.

AU - De Rosa, Maria

AU - De Simone, Giada

AU - Gulotta, Maria R.

AU - Lombino, Jessica

AU - Mekni, Nedra

AU - Perricone, Ugo

AU - Casini, Arturo

AU - Embree, Amanda

AU - Gordon, D. Benjamin

AU - Lei, David

AU - Pratt, Katelin

AU - Voigt, Christopher A.

AU - Chen, Kuang Yu

AU - Jacob, Yves

AU - Krischuns, Tim

AU - Lafaye, Pierre

AU - Zettor, Agnès

AU - Rodríguez, M. Luis

AU - White, Kris M.

AU - Fearon, Daren

AU - Von Delft, Frank

AU - Walsh, Martin A.

AU - Horvath, Dragos

AU - Brooks, Charles L.

AU - Falsafi, Babak

AU - Ford, Bryan

AU - García-Sastre, Adolfo

AU - Yup Lee, Sang

AU - Naffakh, Nadia

AU - Varnek, Alexandre

AU - Klambauer, Günter

AU - Hermans, Thomas M.

PY - 2024/1

Y1 - 2024/1

N2 - 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.

AB - 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.

KW - COVID-19

KW - SARS-CoV-2

KW - drug discovery

KW - machine learning

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UR - http://www.scopus.com/inward/citedby.url?scp=85176949170&partnerID=8YFLogxK

U2 - 10.1002/minf.202300262

DO - 10.1002/minf.202300262

M3 - Article

C2 - 37833243

AN - SCOPUS:85176949170

SN - 1868-1743

VL - 43

JO - Molecular Informatics

JF - Molecular Informatics

IS - 1

M1 - e202300262

ER -

A community effort in SARS-CoV-2 drug discovery

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