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Updated: Jul 30, 2025
Author Spotlight: Investigating the Effects of Compounds on Intestinal Tissue Using 3D Human Cell Line Models
Published on: September 1, 2023
Evaluation of 3D Human Intestinal Organoids as a Platform for EV-A71 Antiviral Drug Discovery
Fatma Masmoudi1,2, Nanci Santos-Ferreira3, Dasja Pajkrt4
1Charles River Laboratories, 2333 CR Leiden, The Netherlands.
Abstract:
Enteroviruses are a leading cause of upper respiratory tract, gastrointestinal, and neurological infections. Management of enterovirus-related diseases has been hindered by the lack of specific antiviral treatment. The pre-clinical and clinical development of such antivirals has been challenging, calling for novel model systems and strategies to identify suitable pre-clinical candidates. Organoids represent a new and outstanding opportunity to test antiviral agents in a more physiologically relevant system. However, dedicated studies addressing the validation and direct comparison of organoids versus commonly used cell lines are lacking. Here, we described the use of human small intestinal organoids (HIOs) as a model to study antiviral treatment against human enterovirus 71 (EV-A71) infection and compared this model to EV-A71-infected RD cells. We used reference antiviral compounds such as enviroxime, rupintrivir, and 2'-C-methylcytidine (2'CMC) to assess their effects on cell viability, virus-induced cytopathic effect, and viral RNA yield in EV-A71-infected HIOs and cell line. The results indicated a difference in the activity of the tested compounds between the two models, with HIOs being more sensitive to infection and drug treatment. In conclusion, the outcome reveals the value added by using the organoid model in virus and antiviral studies.
Insights
Human intestinal organoids (HIOs) offer a more sensitive model for studying enterovirus infections and testing antiviral drugs compared to traditional cell lines. This highlights organoids as a valuable tool for developing new treatments.
Area of Science:
- Virology
- Infectious Diseases
- Drug Discovery
Background:
- Enteroviruses cause significant upper respiratory, gastrointestinal, and neurological infections.
- Effective antiviral treatments for enterovirus infections are lacking, hindering disease management.
- Novel model systems are crucial for identifying promising antiviral drug candidates.
Purpose of the Study:
- To validate human small intestinal organoids (HIOs) as a model for studying antiviral treatments against enterovirus 71 (EV-A71).
- To compare the efficacy of antiviral compounds in HIOs versus conventional cell lines (RD cells).
Main Methods:
- EV-A71 infection was established in both HIOs and RD cells.
- The antiviral activity of enviroxime, rupintrivir, and 2'-C-methylcytidine (2'CMC) was assessed.
- Key metrics included cell viability, virus-induced cytopathic effects, and viral RNA yield.
Main Results:
- A differential activity of antiviral compounds was observed between HIOs and RD cells.
- HIOs demonstrated increased sensitivity to both EV-A71 infection and antiviral drug treatment.
- Organoid models provide a more accurate representation of in vivo antiviral responses.
Conclusions:
- Human intestinal organoids (HIOs) represent a superior model for enterovirus research and antiviral drug screening.
- The study underscores the importance of physiologically relevant models in preclinical antiviral development.
- Organoids enhance the evaluation of antiviral efficacy, offering valuable insights beyond traditional cell lines.
