Journal Article

FZJ-2025-01027

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A community effort to discover small molecule SARS-CoV-2 inhibitors

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. ; Kornoushenko, Y. V. ; Shuldau, M. ; Yushkevich, A. ; Benabderrahmane, M. B. ; Bousquet-Melou, P. ; Bureau, R. ; Charton, B. ; Cirou, B. C. ; Gil, G. ; Allen, W. J. ; Sirimulla, S. ; Watowich, S. ; Antonopoulos, N. A. ; Epitropakis, N. E. ; Krasoulis, A. K. ; Pitsikalis, V. P. ; Theodorakis, S. T. ; 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, K. Y. J. ; Bengio, E. ; Bengio, Y. ; Jain, M. J. ; Korablyov, M. ; Liu, C.-H. ; Marcou, G. ; Glaab, E. ; Barnsley, K. ; Iyengar, S. M. ; Ondrechen, M. J. ; Haupt, V. J. ; Kaiser, F. ; Schroeder, M. ; Pugliese, L. ; Albani, S.FZJ* ; Athanasiou, C. ; Beccari, A. ; Carloni, P.FZJ* ; D'Arrigo, G. ; Gianquinto, E. ; Goßen, J. ; Hanke, A. ; Joseph, B. P.FZJ* ; Kokh, D. B. ; Kovachka, S. ; Manelfi, C. ; Mukherjee, G. ; Muñiz-Chicharro, A. ; Musiani, F. ; Nunes-Alves, A. ; Paiardi, G. ; Rossetti, G.FZJ* ; Sadiq, S. K. ; Spyrakis, F. ; Talarico, C. ; Tsengenes, A. ; Wade, R. C. ; Copeland, C. ; Gaiser, J. ; Olson, D. R. ; Roy, A. ; Venkatraman, V. ; Wheeler, T. J. ; Arthanari, H. ; Blaschitz, K. ; Cespugli, M. ; Durmaz, V. ; Fackeldey, K. ; Fischer, P. D. ; Gorgulla, C. ; Gruber, C. ; Gruber, K. ; Hetmann, M. ; Kinney, J. E. ; Padmanabha Das, K. M. ; Pandita, S. ; Singh, A. ; Steinkellner, G. ; Tesseyre, G. ; Wagner, G. ; Wang, Z.-F. ; Yust, R. J. ; Druzhilovskiy, D. S. ; Filimonov, D. A. ; Pogodin, P. V. ; Poroikov, V. ; Rudik, A. V. ; Stolbov, L. A. ; Veselovsky, A. V. ; De Rosa, M. ; De Simone, G. ; Gulotta, M. R. ; Lombino, J. ; Mekni, N. ; Perricone, U. ; Casini, A. ; Embree, A. ; Gordon, D. B. ; Lei, D. ; Pratt, K. ; Voigt, C. A. ; Chen, K.-Y. ; Jacob, Y. ; Krischuns, T. ; Lafaye, P. ; Zettor, A. ; Rodríguez, M. L. ; White, K. M. ; Fearon, D. ; Von Delft, F. ; Walsh, M. A. ; Horvath, D. ; Brooks III, C. L. ; Falsafi, B. ; Ford, B. ; García-Sastre, A. ; Lee, S. Y. ; Naffakh, N. ; Varnek, A. ; Klambauer, G. ; Hermans, T. M. (Corresponding author)

2024
Wiley-VCH-Verl. Weinheim

This record in other databases:      

Please use a persistent id in citations: doi:10.26434/chemrxiv-2023-1d5w8  doi:10.1002/minf.202300262  doi:10.34734/FZJ-2025-01027

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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Contributing Institute(s):

1. Computational Biomedicine (INM-9)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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