Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids

Krueger, J.; Gross, R.; Conzelmann, C.; Mueller, J. A.; Koepke, L.; Sparrer, K.; Schuetz, D.; Seufferlein, T.; Barth, T. F. E.; Stenger, S.; Heller, S.; Kleger, A.; Muench, J.

doi:10.1101/2020.06.10.144816

bioRxiv · 10.1101/2020.06.10.144816

Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids

Krueger, J.·Gross, R.·Conzelmann, C.·Mueller, J. A.·Koepke, L.·Sparrer, K.·Schuetz, D.·Seufferlein, T.·Barth, T. F. E.·Stenger, S.·Heller, S.·Kleger, A.·Muench, J.

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Abstract

Gastrointestinal symptoms in COVID-19 are associated with prolonged symptoms and increased severity. We employed human intestinal organoids derived from pluripotent stem cells (PSC-HIOs) to analyze SARS-CoV-2 pathogenesis and to validate efficacy of specific drugs in the gut. Certain, but not all cell types in PSC-HIOs express SARS-CoV-2 entry factors ACE2 and TMPRSS2, rendering them susceptible to SARS-CoV-2 infection. Remdesivir, a promising drug to treat COVID-19, effectively suppressed SARS-CoV-2 infection of PSC-HIOs. In contrast, the histamine-2-blocker famotidine showed no effect. Thus, PSC-HIOs provide an interesting platform to study SARS-CoV-2 infection and to identify or validate drugs.

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Krueger, J., Gross, R., Conzelmann, C., Mueller, J. A., Koepke, L., Sparrer, K., Schuetz, D., Seufferlein, T., Barth, T. F. E., Stenger, S., Heller, S., Kleger, A., Muench, J.. 2020-06-11. Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids. https://doi.org/10.1101/2020.06.10.144816

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