Cytopathic SARS-CoV-2 screening on VERO-E6 cells in a large-scale repurposing effort.

Autor: Zaliani A; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525, Hamburg, Germany. andrea.zaliani@itmp.fraunhofer.de.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany. andrea.zaliani@itmp.fraunhofer.de., Vangeel L; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium., Reinshagen J; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525, Hamburg, Germany.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Iaconis D; Dompé Farmaceutici SpA, via Campo di Pile, 67100, L'Aquila, Italy., Kuzikov M; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525, Hamburg, Germany.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Keminer O; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525, Hamburg, Germany.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Wolf M; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525, Hamburg, Germany.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Ellinger B; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525, Hamburg, Germany.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Esposito F; Dipartimento di Scienze della vita e dell'ambiente, Cittadella Universitaria di Monserrato, SS554, 09042, Monserrato, Cagliari, Italy., Corona A; Dipartimento di Scienze della vita e dell'ambiente, Cittadella Universitaria di Monserrato, SS554, 09042, Monserrato, Cagliari, Italy., Tramontano E; Dipartimento di Scienze della vita e dell'ambiente, Cittadella Universitaria di Monserrato, SS554, 09042, Monserrato, Cagliari, Italy., Manelfi C; Dompé Farmaceutici SpA, via Campo di Pile, 67100, L'Aquila, Italy., Herzog K; EU-OPENSCREEN ERIC, Campus Berlin Buch, Robert-Rössle-Str. 10, 13125, Berlin, Germany., Jochmans D; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium., De Jonghe S; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium., Chiu W; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium., Francken T; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium., Schepers J; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium., Collard C; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium., Abbasi K; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium., Claussen C; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525, Hamburg, Germany.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Summa V; Department of Excellence of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy., Beccari AR; Dompé Farmaceutici SpA, via Campo di Pile, 67100, L'Aquila, Italy., Neyts J; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium., Gribbon P; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525, Hamburg, Germany.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany., Leyssen P; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - box 1043, 3000, Leuven, Belgium.
Jazyk: angličtina
Zdroj: Scientific data [Sci Data] 2022 Jul 13; Vol. 9 (1), pp. 405. Date of Electronic Publication: 2022 Jul 13.
DOI: 10.1038/s41597-022-01532-x
Abstrakt: Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC 50  < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
(© 2022. The Author(s).)
Databáze: MEDLINE
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