Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation.

Autor: Serra A; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; BioMediTech Institute, Tampere University, Tampere, Finland.; Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland., Fratello M; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; BioMediTech Institute, Tampere University, Tampere, Finland.; Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland., Federico A; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; BioMediTech Institute, Tampere University, Tampere, Finland.; Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland., Ojha R; Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Provenzani R; Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland., Tasnadi E; Synthetic and Systems Biology Unit, Biological Research Centre, Eotvos Lorand Research Network, Szeged, Hungary., Cattelani L; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; BioMediTech Institute, Tampere University, Tampere, Finland.; Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland., Del Giudice G; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; BioMediTech Institute, Tampere University, Tampere, Finland.; Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland., Kinaret PAS; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; BioMediTech Institute, Tampere University, Tampere, Finland.; Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland.; Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Saarimäki LA; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; BioMediTech Institute, Tampere University, Tampere, Finland.; Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland., Pavel A; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; BioMediTech Institute, Tampere University, Tampere, Finland.; Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland., Kuivanen S; Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Cerullo V; Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland., Vapalahti O; Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.; Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Horvath P; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.; Synthetic and Systems Biology Unit, Biological Research Centre, Eotvos Lorand Research Network, Szeged, Hungary., Lieto AD; Department of Forensic Psychiatry, Aarhus University, Aarhus, Denmark., Yli-Kauhaluoma J; Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland., Balistreri G; Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Queensland Brain Institute, The University of Queensland, Brisbane, Australia., Greco D; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; BioMediTech Institute, Tampere University, Tampere, Finland.; Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland.; Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Jazyk: angličtina
Zdroj: Briefings in bioinformatics [Brief Bioinform] 2022 Jan 17; Vol. 23 (1).
DOI: 10.1093/bib/bbab507
Abstrakt: The pharmacological arsenal against the COVID-19 pandemic is largely based on generic anti-inflammatory strategies or poorly scalable solutions. Moreover, as the ongoing vaccination campaign is rolling slower than wished, affordable and effective therapeutics are needed. To this end, there is increasing attention toward computational methods for drug repositioning and de novo drug design. Here, multiple data-driven computational approaches are systematically integrated to perform a virtual screening and prioritize candidate drugs for the treatment of COVID-19. From the list of prioritized drugs, a subset of representative candidates to test in human cells is selected. Two compounds, 7-hydroxystaurosporine and bafetinib, show synergistic antiviral effects in vitro and strongly inhibit viral-induced syncytia formation. Moreover, since existing drug repositioning methods provide limited usable information for de novo drug design, the relevant chemical substructures of the identified drugs are extracted to provide a chemical vocabulary that may help to design new effective drugs.
(© The Author(s) 2021. Published by Oxford University Press.)
Databáze: MEDLINE
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