دورية أكاديمية
Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform
| العنوان: | Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform |
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| المؤلفون: | Bojkova, Denisa, Reus, Philipp, Panosch, Leona, Bechtel, Marco, Rothenburger, Tamara, Kandler, Joshua D., Pfeiffer, Annika Eby, Wagner, Julian Uwe Gabriel, Shumliakivska, Mariana, Dimmeler, Stefanie, Olmer, Ruth Maria, Martin, Ulrich, Vondran, Florian, Toptan, Tuna, Rothweiler, Florian, Zehner, Richard, Rabenau, Holger, Osman, Karen L., Pullan, Steven T., Carroll, Miles, Stack, Richard, Ciesek, Sandra, Wass, Mark N., Michaelis, Martin, Cinatl, Jindrich |
| سنة النشر: | 2023 |
| المجموعة: | Publication Server of Goethe University Frankfurt am Main |
| مصطلحات موضوعية: | ddc:610 |
| الوصف: | Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a readout for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in numerous cell culture models, independently of cytopathogenic effect formation. Compared to other models, the Caco-2 subline Caco-2-F03 displayed superior performance. It possesses a stable SARS-CoV-2 susceptibility phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1,796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of phosphoglycerate dehydrogenase (PHGDH), CDC like kinase 1 (CLK-1), and colony stimulating factor 1 receptor (CSF1R). The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the hexokinase II (HK2) inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2-F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false-positive hits. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/zip |
| اللغة: | English |
| العلاقة: | http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73350Test; urn:nbn:de:hebis:30:3-733509; https://nbn-resolving.org/urn:nbn:de:hebis:30:3-733509Test; https://doi.org/10.1016/j.isci.2023.105944Test; http://publikationen.ub.uni-frankfurt.de/files/73350/container.zipTest |
| DOI: | 10.1016/j.isci.2023.105944 |
| الإتاحة: | https://doi.org/10.1016/j.isci.2023.105944Test http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73350Test https://nbn-resolving.org/urn:nbn:de:hebis:30:3-733509Test http://publikationen.ub.uni-frankfurt.de/files/73350/container.zipTest |
| حقوق: | http://creativecommons.org/licenses/by-nc-nd/4.0/de/deed.deTest ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6873DF6B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.isci.2023.105944 |
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