Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids
GI drug discovery/repurposing immunology/immunity therapeutics
Authors: Krüger, J,. et al
Link to paper: https://doi.org/10.1101/2020.06.10.144816
Journal/ Pre-Print:bioRxiv preprint
Tags: Immunology/Immunity, Gut, Stem Cells, Therapeutics
Pluripotent stem cell derived-Human intestinal organoids (PSC-HIO) support productive infection with SARS-CoV2 in a cell-type specific manner
Remdesivir and EKI, but not famotidine impedes SARS-CoV2 pathogenesis in PSC-HIOs
SARS-CoV2, with the exception of goblet cells, productively infects different epithelial cell types. Enteroendocrine cells in addition to enterocytes were infected by SARS-CoV2 indicating that the virus affects hormone secretion.
The authors report that SARS-CoV2 in addition to infecting only the enterocytes (Lamers MM, et al. Science 2020) as previously reported, also infect the other epithelial sub-types such as enteroendocrine cells and paneth cells in gastrointestinal tissue, with various intensity. Goblet cells display weak ACE2 expression and are not productively infected by SARS-CoV2. In vitro differentiated PSC-HIOs provide a better 3D model system for drug testing over the traditional stem cell derived intestinal organoids as they express multiple cell types. Additionally, the authors report that Remdesivir and EK1 block SARS-CoV2 pathogenesis in PSC-HIOs.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Understand the virology and/or cell biology of SARS-CoV2/COVID19
Inhibit of SARS-CoV2/COVID19 transmission
In vitro study
Strengths and limitations of the paper
Novelty: SARS-CoV2 infects multiple cell types in the gastrointestinal tissue in addition to just the enterocytes as previously reported.
Standing in the field:Provides additional information on different epithelial cell types of the gastrointestinal tissue infected by SARS-CoV2
Appropriate statistics: Mostly a descriptive study stating that SARS-CoV2 productively infects multiple intestinal epithelial cell types. Since there was no mention of technical or biological replicates, difficult to assess the statistics employed.
Viral model used:BetaCoV/Netherlands/01/NL/2020
Translatability:Not close to translational potential yet. But the PSC-HIO model described can be a viable tool for compound testing
1. No mention of technical/biological replicates giving rise to the question of reproducibility.
2. More immunofluorescent pictures required to verify virus infectivity of the organoids.