Human airway organoids as a high-throughput screening platform for antiviral natural products discovery

Hubert, M.; Haemmerli, P.; Marcourt, L.; Lara-Quintero, E.; Arthaud, L.; Quiros-Guerrero, L.-M.; Donnaray, S.; Rimensberger, K.; Gaudry, A.; Alessandri, E.; Stroulios, G.; Cambet, Y.; Prodon, F.; Maco, B.; Constant, S.; Simmini, S.; Grondin, A.; Queiroz, E. F.; Clement, S.; Wolfender, J.-L.; Tapparel, C.

doi:10.64898/2026.02.04.703746

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bioRxiv · 10.64898/2026.02.04.703746

Human airway organoids as a high-throughput screening platform for antiviral natural products discovery

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Abstract

Antiviral drug discovery for respiratory viruses is hindered by the lack of scalable physiologically relevant systems. Here, we report the first high-throughput screen of 764 natural plant extracts against respiratory syncytial virus (RSV) using human primary airway organoids as a relevant model. A parallel screen conducted in A549 cells allowed the identification of 70 extracts with organoid-specific antiviral activity from which 45 active phytocompounds were purified. We identified early- and late-acting antiviral compounds and demonstrated a polarization-dependent activity for some of them. Collectively, our results establish the use of airway organoids as a scalable first-line platform for high-throughput antiviral discovery and exploit the plant-derived chemical space as an underexplored source of RSV inhibitors.

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Hubert, M., Haemmerli, P., Marcourt, L., Lara-Quintero, E., Arthaud, L., Quiros-Guerrero, L.-M., Donnaray, S., Rimensberger, K., Gaudry, A., Alessandri, E., Stroulios, G., Cambet, Y., Prodon, F., Maco, B., Constant, S., Simmini, S., Grondin, A., Queiroz, E. F., Clement, S., Wolfender, J.-L., Tapparel, C.. 2026-02-04. Human airway organoids as a high-throughput screening platform for antiviral natural products discovery. https://doi.org/10.64898/2026.02.04.703746

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