IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44339-z.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44339-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-44339-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Dominik Kiemel & Ann-Sophie Helene Kroell & Solène Denolly & Uta Haselmann & Jean-François Bonfanti & Jose Ignacio Andres & Brahma Ghosh & Peggy Geluykens & Suzanne J. F. Kaptein & Lucas Wilken & Piet, 2024. "Pan-serotype dengue virus inhibitor JNJ-A07 targets NS4A-2K-NS4B interaction with NS2B/NS3 and blocks replication organelle formation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Lisa-Marie Funk & Gereon Poschmann & Fabian Rabe von Pappenheim & Ashwin Chari & Kim M. Stegmann & Antje Dickmanns & Marie Wensien & Nora Eulig & Elham Paknia & Gabi Heyne & Elke Penka & Arwen R. Pear, 2024. "Multiple redox switches of the SARS-CoV-2 main protease in vitro provide opportunities for drug design," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Svenja M. Sake & Xiaoyu Zhang & Manoj Kumar Rajak & Melanie Urbanek-Quaing & Arnaud Carpentier & Antonia P. Gunesch & Christina Grethe & Alina Matthaei & Jessica Rückert & Marie Galloux & Thibaut Larc, 2024. "Drug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Daniel W. Kneller & Hui Li & Gwyndalyn Phillips & Kevin L. Weiss & Qiu Zhang & Mark A. Arnould & Colleen B. Jonsson & Surekha Surendranathan & Jyothi Parvathareddy & Matthew P. Blakeley & Leighton Coa, 2022. "Covalent narlaprevir- and boceprevir-derived hybrid inhibitors of SARS-CoV-2 main protease," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Zhanding Cui & Jinlong Liu & Chong Xie & Tao Wang & Pu Sun & Jinlong Wang & Jiaoyang Li & Guoxiu Li & Jicheng Qiu & Ying Zhang & Dengliang Li & Ying Sun & Juanbin Yin & Kun Li & Zhixun Zhao & Hong Yua, 2024. "High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. J. Ross Terrell & Thao T. Le & Ananya Paul & Margo A. Brinton & W. David Wilson & Gregory M. K. Poon & Markus W. Germann & Jessica L. Siemer, 2024. "Structure of an RNA G-quadruplex from the West Nile virus genome," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44339-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.