Transcriptional Effects of Candidate COVID-19 Treatments on Cardiac Myocytes

Tobias Jakobi, Julia Groß, Lukas Cyganek, Shirin Doroudgar

Research output: Contribution to journalArticlepeer-review


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 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.

Original languageEnglish (US)
Article number844441
JournalFrontiers in Cardiovascular Medicine
StatePublished - May 24 2022


  • COVID-19
  • SARS-CoV-2
  • cardiac myocytes
  • chloroquine
  • hydroxychloroquine
  • lopinavir
  • remdesevir
  • ritonavir

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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