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Multiplexed multicolor antiviral assay amenable for high-throughput research

Author

Listed:
  • Li-Hsin Li

    (Laboratory of Virology and Chemotherapy
    Molecular Vaccinology and Vaccine Discovery group)

  • Winston Chiu

    (Laboratory of Virology and Chemotherapy)

  • Yun-An Huang

    (Laboratory for Circuit Neuroscience
    Neuro-Electronics Research Flanders (NERF))

  • Madina Rasulova

    (Translational Platform Virology and Chemotherapy (TPVC))

  • Thomas Vercruysse

    (Translational Platform Virology and Chemotherapy (TPVC)
    AstriVax)

  • Hendrik Jan Thibaut

    (Translational Platform Virology and Chemotherapy (TPVC))

  • Sebastiaan ter Horst

    (Laboratory of Virology and Chemotherapy
    Cerba Research)

  • Joana Rocha-Pereira

    (Laboratory of Virology and Chemotherapy)

  • Greet Vanhoof

    (Janssen Pharmaceutica)

  • Doortje Borrenberghs

    (Janssen Pharmaceutica)

  • Olivia Goethals

    (Janssen Pharmaceutica)

  • Suzanne J. F. Kaptein

    (Laboratory of Virology and Chemotherapy)

  • Pieter Leyssen

    (Laboratory of Virology and Chemotherapy)

  • Johan Neyts

    (Laboratory of Virology and Chemotherapy)

  • Kai Dallmeier

    (Laboratory of Virology and Chemotherapy
    Molecular Vaccinology and Vaccine Discovery group)

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.

Suggested Citation

  • Li-Hsin Li & Winston Chiu & Yun-An Huang & Madina Rasulova & Thomas Vercruysse & Hendrik Jan Thibaut & Sebastiaan ter Horst & Joana Rocha-Pereira & Greet Vanhoof & Doortje Borrenberghs & Olivia Goetha, 2024. "Multiplexed multicolor antiviral assay amenable for high-throughput research," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44339-z
    DOI: 10.1038/s41467-023-44339-z
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    References listed on IDEAS

    as
    1. Olivia Goethals & Suzanne J. F. Kaptein & Bart Kesteleyn & Jean-François Bonfanti & Liesbeth Wesenbeeck & Dorothée Bardiot & Ernst J. Verschoor & Babs E. Verstrepen & Zahra Fagrouch & J. Robert Putnak, 2023. "Blocking NS3–NS4B interaction inhibits dengue virus in non-human primates," Nature, Nature, vol. 615(7953), pages 678-686, March.
    2. Laura Riva & Shuofeng Yuan & Xin Yin & Laura Martin-Sancho & Naoko Matsunaga & Lars Pache & Sebastian Burgstaller-Muehlbacher & Paul D. Jesus & Peter Teriete & Mitchell V. Hull & Max W. Chang & Jasper, 2020. "Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing," Nature, Nature, vol. 586(7827), pages 113-119, October.
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