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  • 2022Journal Article
    [["dc.bibliographiccitation.artnumber","844441"],["dc.bibliographiccitation.journal","Frontiers in Cardiovascular Medicine"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Jakobi, Tobias"],["dc.contributor.author","Groß, Julia"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Doroudgar, Shirin"],["dc.date.accessioned","2022-07-01T07:35:28Z"],["dc.date.available","2022-07-01T07:35:28Z"],["dc.date.issued","2022"],["dc.description.abstract","Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has emerged as a major cause of morbidity and mortality worldwide, placing unprecedented pressure on healthcare. Cardiomyopathy is described in patients with severe COVID-19 and increasing evidence suggests that cardiovascular involvement portends a high mortality. To facilitate fast development of antiviral interventions, drugs initially developed to treat other diseases are currently being repurposed as COVID-19 treatments. While it has been shown that SARS-CoV-2 invades cells through the angiotensin-converting enzyme 2 receptor (ACE2), the effect of drugs currently repurposed to treat COVID-19 on the heart requires further investigation. Methods Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) were treated with five repurposed drugs (remdesivir, lopinavir/ritonavir, lopinavir/ritonavir/interferon beta (INF-β), hydroxychloroquine, and chloroquine) and compared with DMSO controls. Transcriptional profiling was performed to identify global changes in gene expression programs. Results RNA sequencing of hiPSC-CMs revealed significant changes in gene programs related to calcium handling and the endoplasmic reticulum stress response, most prominently for lopinavir/ritonavir and lopinavir/ritonavir/interferon-beta. The results of the differential gene expression analysis are available for interactive access at https://covid19drugs.jakobilab.org . Conclusion Transcriptional profiling in hiPSC-CMs treated with COVID-19 drugs identified unfavorable changes with lopinavir/ritonavir and lopinavir/ritonavir/INF-β in key cardiac gene programs that may negatively affect heart function."],["dc.identifier.doi","10.3389/fcvm.2022.844441"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112179"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","2297-055X"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Transcriptional Effects of Candidate COVID-19 Treatments on Cardiac Myocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]
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