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

Jana Krüger, Rüdiger Groß, Carina Conzelmann, Janis A. Müller, Lennart Koepke, Konstantin M. J. Sparrer, Desiree Schütz, Thomas Seufferlein, Thomas F.E. Barth, Steffen Stenger, Sandra Heller, Alexander Kleger, Jan Münch
doi: https://doi.org/10.1101/2020.06.10.144816
Jana Krüger
1Department of Internal Medicine 1, Ulm University Hospital, Albert-Einstein-Allee 23, Ulm, Germany
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Rüdiger Groß
2Institute of Molecular Virology, Ulm University Medical Centre, Meyerhofstrasse 1, Ulm, Germany
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Carina Conzelmann
2Institute of Molecular Virology, Ulm University Medical Centre, Meyerhofstrasse 1, Ulm, Germany
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Janis A. Müller
2Institute of Molecular Virology, Ulm University Medical Centre, Meyerhofstrasse 1, Ulm, Germany
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Lennart Koepke
2Institute of Molecular Virology, Ulm University Medical Centre, Meyerhofstrasse 1, Ulm, Germany
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Konstantin M. J. Sparrer
2Institute of Molecular Virology, Ulm University Medical Centre, Meyerhofstrasse 1, Ulm, Germany
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Desiree Schütz
2Institute of Molecular Virology, Ulm University Medical Centre, Meyerhofstrasse 1, Ulm, Germany
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Thomas Seufferlein
1Department of Internal Medicine 1, Ulm University Hospital, Albert-Einstein-Allee 23, Ulm, Germany
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Thomas F.E. Barth
3Department of Pathology, Ulm University Hospital, Albert-Einstein-Allee 23, Ulm, Germany
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Steffen Stenger
4Institute for Microbiology and Hygiene, Ulm University Medical Center, Ulm 89081, Germany
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Sandra Heller
1Department of Internal Medicine 1, Ulm University Hospital, Albert-Einstein-Allee 23, Ulm, Germany
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Alexander Kleger
1Department of Internal Medicine 1, Ulm University Hospital, Albert-Einstein-Allee 23, Ulm, Germany
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  • For correspondence: jan.muench@uni-ulm.de alexander.kleger@uni-ulm.de
Jan Münch
2Institute of Molecular Virology, Ulm University Medical Centre, Meyerhofstrasse 1, Ulm, Germany
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  • For correspondence: jan.muench@uni-ulm.de alexander.kleger@uni-ulm.de
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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.

Competing Interest Statement

The authors have declared no competing interest.

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  • Conflict of interest statement The authors have no conflicts of interest to declare.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 11, 2020.
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Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids
Jana Krüger, Rüdiger Groß, Carina Conzelmann, Janis A. Müller, Lennart Koepke, Konstantin M. J. Sparrer, Desiree Schütz, Thomas Seufferlein, Thomas F.E. Barth, Steffen Stenger, Sandra Heller, Alexander Kleger, Jan Münch
bioRxiv 2020.06.10.144816; doi: https://doi.org/10.1101/2020.06.10.144816
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Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids
Jana Krüger, Rüdiger Groß, Carina Conzelmann, Janis A. Müller, Lennart Koepke, Konstantin M. J. Sparrer, Desiree Schütz, Thomas Seufferlein, Thomas F.E. Barth, Steffen Stenger, Sandra Heller, Alexander Kleger, Jan Münch
bioRxiv 2020.06.10.144816; doi: https://doi.org/10.1101/2020.06.10.144816

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