In conclusion, these results validate CDCA-treated cholangiocyte organoids as a platform for disease modelling and drug testing against SARS-CoV-2 infection, identify FXR as a therapeutic target in the management of COVID-19 and open up new avenues for the modulation of ACE2 through FXR for the prevention of infection with SARS-CoV-2 as well as other viruses that use ACE2 for cell entry. Here, NR1H4 is linked to COVID-19.