Transcriptional effects of candidate COVID-19 treatments on cardiac myocytes

• Verfasst von: Jakobi, Tobias [VerfasserIn]
• Verfasst von: Groß, Julia [VerfasserIn]
• Verfasst von: Cyganek, Lukas [VerfasserIn]
• Verfasst von: Doroudgar, Shirin [VerfasserIn]
• Titel: Transcriptional effects of candidate COVID-19 treatments on cardiac myocytes
• Verf.angabe: Tobias Jakobi, Julia Groß, Lukas Cyganek and Shirin Doroudgar
• E-Jahr: 2022
• Jahr: 24 May 2022
• Umfang: 13 S.
• Fussnoten: This article is part of the Research Topic "What do we know about COVID-19 implications for cardiovascular disease?" ; Gesehen am 06.07.2022
• Titel Quelle: Enthalten in: Frontiers in Cardiovascular Medicine
• Ort Quelle: Lausanne : Frontiers Media, 2014
• Jahr Quelle: 2022
• Band/Heft Quelle: 9(2022), Artikel-ID 844441, Seite 1-13
• ISSN Quelle: 2297-055X
• DOI: doi:10.3389/fcvm.2022.844441
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 180929648X

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.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.