A flexible, image-based, high-throughput platform encompassing in-depth cell profiling to identify broad-spectrum coronavirus antivirals with limited off-target effects
Copyright © 2023. Published by Elsevier B.V..
The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a major threat to global health. Although the World Health Organization ended the public health emergency status, antiviral drugs are needed to address new variants of SARS-CoV-2 and future pandemics. To identify novel broad-spectrum coronavirus drugs, we developed a high-content imaging platform compatible with high-throughput screening. The platform is broadly applicable as it can be adapted to include various cell types, viruses, antibodies, and dyes. We demonstrated that the antiviral activity of compounds against SARS-CoV-2 variants (Omicron BA.5 and Omicron XBB.1.5), SARS-CoV, and human coronavirus 229E could easily be assessed. The inclusion of cellular dyes and immunostaining in combination with in-depth image analysis enabled us to identify compounds that induced undesirable phenotypes in host cells, such as changes in cell morphology or in lysosomal activity. With the platform, we screened ∼900K compounds and triaged hits, thereby identifying potential candidate compounds carrying broad-spectrum activity with limited off-target effects. The flexibility and early-stage identification of compounds with limited host cell effects provided by this high-content imaging platform can facilitate coronavirus drug discovery. We anticipate that its rapid deployability and fast turnaround can also be applied to combat future pandemics.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:222 |
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| Enthalten in: |
Antiviral research - 222(2024) vom: 01. Feb., Seite 105789 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Doijen, Jordi [VerfasserIn] |
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| Links: |
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| Themen: |
Antiviral Agents |
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| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 22.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.antiviral.2023.105789 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366487787 |
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| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a major threat to global health. Although the World Health Organization ended the public health emergency status, antiviral drugs are needed to address new variants of SARS-CoV-2 and future pandemics. To identify novel broad-spectrum coronavirus drugs, we developed a high-content imaging platform compatible with high-throughput screening. The platform is broadly applicable as it can be adapted to include various cell types, viruses, antibodies, and dyes. We demonstrated that the antiviral activity of compounds against SARS-CoV-2 variants (Omicron BA.5 and Omicron XBB.1.5), SARS-CoV, and human coronavirus 229E could easily be assessed. The inclusion of cellular dyes and immunostaining in combination with in-depth image analysis enabled us to identify compounds that induced undesirable phenotypes in host cells, such as changes in cell morphology or in lysosomal activity. With the platform, we screened ∼900K compounds and triaged hits, thereby identifying potential candidate compounds carrying broad-spectrum activity with limited off-target effects. The flexibility and early-stage identification of compounds with limited host cell effects provided by this high-content imaging platform can facilitate coronavirus drug discovery. We anticipate that its rapid deployability and fast turnaround can also be applied to combat future pandemics | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Heo, Inha |e verfasserin |4 aut | |
| 700 | 1 | |a Temmerman, Koen |e verfasserin |4 aut | |
| 700 | 1 | |a Vermeulen, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Diels, Annick |e verfasserin |4 aut | |
| 700 | 1 | |a Jaensch, Steffen |e verfasserin |4 aut | |
| 700 | 1 | |a Burcin, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Van den Broeck, Nick |e verfasserin |4 aut | |
| 700 | 1 | |a Raeymaekers, Valerie |e verfasserin |4 aut | |
| 700 | 1 | |a Peremans, Joren |e verfasserin |4 aut | |
| 700 | 1 | |a Konings, Katrien |e verfasserin |4 aut | |
| 700 | 1 | |a Clement, Maxime |e verfasserin |4 aut | |
| 700 | 1 | |a Peeters, Danielle |e verfasserin |4 aut | |
| 700 | 1 | |a Van Loock, Marnix |e verfasserin |4 aut | |
| 700 | 1 | |a Koul, Anil |e verfasserin |4 aut | |
| 700 | 1 | |a Buyck, Christophe |e verfasserin |4 aut | |
| 700 | 1 | |a Van Gool, Michiel |e verfasserin |4 aut | |
| 700 | 1 | |a Van Damme, Ellen |e verfasserin |4 aut | |
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