Transcriptional effects of candidate COVID-19 treatments on cardiac myocytes
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...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
24 May 2022
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| In: |
Frontiers in Cardiovascular Medicine
Year: 2022, Volume: 9, Pages: 1-13 |
| ISSN: | 2297-055X |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fcvm.2022.844441
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| Author Notes: | Tobias Jakobi, Julia Groß, Lukas Cyganek and Shirin Doroudgar |
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| 245 | 1 | 0 | |a Transcriptional effects of candidate COVID-19 treatments on cardiac myocytes |c Tobias Jakobi, Julia Groß, Lukas Cyganek and Shirin Doroudgar |
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| 520 | |a 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.MethodsHuman 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.ResultsRNA 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.ConclusionTranscriptional 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. | ||
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| 700 | 1 | |a Doroudgar, Shirin |e VerfasserIn |0 (DE-588)1139390260 |0 (DE-627)897138023 |0 (DE-576)493250972 |4 aut | |
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