Multiplexed multicolor antiviral assay amenable for high-throughput research.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 Jan 2024
02 Jan 2024
Historique:
received:
09
02
2023
accepted:
08
12
2023
medline:
4
1
2024
pubmed:
4
1
2024
entrez:
3
1
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38168091
doi: 10.1038/s41467-023-44339-z
pii: 10.1038/s41467-023-44339-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
42Subventions
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : no. 30981113 (VirEOS)
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : no. 30981113 (VirEOS)
Organisme : KU Leuven (Katholieke Universiteit Leuven)
ID : C3/19/057 (Lab of Excellence))
Organisme : KU Leuven (Katholieke Universiteit Leuven)
ID : DBOF/14/062
Organisme : KU Leuven (Katholieke Universiteit Leuven)
ID : C24/18/080
Organisme : KU Leuven (Katholieke Universiteit Leuven)
ID : STG/21/028
Informations de copyright
© 2024. The Author(s).
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