Multiplexed multicolor antiviral assay amenable for high-throughput research.
Nat Commun
; 15(1): 42, 2024 01 02.
Article
em En
| MEDLINE
| ID: mdl-38168091
ABSTRACT
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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Base de dados:
MEDLINE
Assunto principal:
Vírus
/
Viroses
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article