Multiplexed multicolor antiviral assay amenable for high-throughput research
© 2024. The Author(s)..
To curb viral epidemics and pandemics, antiviral drugs are needed with activity against entire genera or families of viruses. Here, we develop a cell-based multiplex antiviral assay for high-throughput screening against multiple viruses at once, as demonstrated by using three distantly related orthoflaviviruses: dengue, Japanese encephalitis and yellow fever virus. Each virus is tagged with a distinct fluorescent protein, enabling individual monitoring in cell culture through high-content imaging. Specific antisera and small-molecule inhibitors are employed to validate that multiplexing approach yields comparable inhibition profiles to single-virus infection assays. To facilitate downstream analysis, a kernel is developed to deconvolute and reduce the multidimensional quantitative data to three cartesian coordinates. The methodology is applicable to viruses from different families as exemplified by co-infections with chikungunya, parainfluenza and Bunyamwera viruses. The multiplex approach is expected to facilitate the discovery of broader-spectrum antivirals, as shown in a pilot screen of approximately 1200 drug-like small-molecules.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 02. Jan., Seite 42 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Li-Hsin [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Completed 05.01.2024 Date Revised 05.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-44339-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM36658720X |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a To curb viral epidemics and pandemics, antiviral drugs are needed with activity against entire genera or families of viruses. Here, we develop a cell-based multiplex antiviral assay for high-throughput screening against multiple viruses at once, as demonstrated by using three distantly related orthoflaviviruses: dengue, Japanese encephalitis and yellow fever virus. Each virus is tagged with a distinct fluorescent protein, enabling individual monitoring in cell culture through high-content imaging. Specific antisera and small-molecule inhibitors are employed to validate that multiplexing approach yields comparable inhibition profiles to single-virus infection assays. To facilitate downstream analysis, a kernel is developed to deconvolute and reduce the multidimensional quantitative data to three cartesian coordinates. The methodology is applicable to viruses from different families as exemplified by co-infections with chikungunya, parainfluenza and Bunyamwera viruses. The multiplex approach is expected to facilitate the discovery of broader-spectrum antivirals, as shown in a pilot screen of approximately 1200 drug-like small-molecules | ||
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| 700 | 1 | |a Thibaut, Hendrik Jan |e verfasserin |4 aut | |
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| 700 | 1 | |a Borrenberghs, Doortje |e verfasserin |4 aut | |
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| 700 | 1 | |a Dallmeier, Kai |e verfasserin |4 aut | |
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