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.
Show 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.
Matching journals
The top 16 journals account for 50% of the predicted probability mass.