Transcriptional Effects of Candidate COVID-19 Treatments on Cardiac Myocytes

Frontiers in Cardiovascular Medicine

article

Tobias Jakobi¹  Julia Groß²  Lukas Cyganek⁴  Shirin Doroudgar¹ 

[1]Department of Internal Medicine and the Translational Cardiovascular Research Center, University of Arizona – College of Medicine – Phoenix

[2]Department of Cardiology, Angiology, and Pneumology, Heidelberg University Hospital

[3]DZHK ,(German Centre for Cardiovascular Research)

[4]Stem Cell Unit, Department of Cardiology and Pneumology, University Medical Center Göttingen

关键词: COVID-19;    SARS-CoV-2;    chloroquine;    hydroxychloroquine;    remdesevir;    ritonavir;    lopinavir;    cardiac myocytes;   

DOI  :  10.3389/fcvm.2022.844441

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY