Evaluation of 3D Human Intestinal Organoids as a Platform for EV-A71 Antiviral Drug Discovery

Cells. 2023 Apr 12;12(8):1138. doi: 10.3390/cells12081138.


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.

Keywords: antivirals; enterovirus; intestinal; organoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Enterovirus A, Human* / physiology
  • Enterovirus Infections* / drug therapy
  • Enterovirus*
  • Humans
  • Organoids


  • Antiviral Agents

Grants and funding

This research was funded by OrganoVIR, grant number 812673. This work was supported by KU Leuven Starting Grant to J.R.-P.