2. Academic Validation
  3. Antiviral activity and safety of remdesivir against SARS-CoV-2 infection in human pluripotent stem cell-derived cardiomyocytes

Antiviral activity and safety of remdesivir against SARS-CoV-2 infection in human pluripotent stem cell-derived cardiomyocytes

  • Antiviral Res. 2020 Dec;184:104955. doi: 10.1016/j.antiviral.2020.104955.
Seong Woo Choi 1,  Jin Soo Shin 2,  Soon-Jung Park 3,  Eunhye Jung 4,  Yun-Gwi Park 3,  Jiho Lee 5,  Sung Joon Kim 1,  Hun-Jun Park 6,  Jung-Hoon Lee 7,  Sung-Min Park 5,  Sung-Hwan Moon 8,  Kiwon Ban 9,  Yun Young Go 10
Affiliations

Affiliations

  • 1 Department of Physiology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 2 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Infectious Disease Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
  • 3 Stem Cell Research Institute, T&R Biofab Co. Ltd, Siheung, Republic of Korea.
  • 4 Infectious Disease Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
  • 5 School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Republic of Korea.
  • 6 Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, Republic of Korea.
  • 7 Department of Chemistry, City University of Hong Kong, Hong Kong SAR, China.
  • 8 Stem Cell Research Institute, T&R Biofab Co. Ltd, Siheung, Republic of Korea; Department of Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea. Electronic address: sunghwanmoon@tnrbiofab.com.
  • 9 Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China. Electronic address: kiwonban@cityu.edu.hk.
  • 10 Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong SAR, China. Electronic address: yunygo@cityu.edu.hk.
PMID: 33091434 DOI: 10.1016/j.antiviral.2020.104955
Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is considered as the most significant global public health crisis of the century. Several drug candidates have been suggested as potential therapeutic options for COVID-19, including remdesivir, currently the only authorized drug for use under an Emergency Use Authorization. However, there is only limited information regarding the safety profiles of the proposed drugs, in particular drug-induced cardiotoxicity. Here, we evaluated the Antiviral activity and cardiotoxicity of remdesivir using cardiomyocytes-derived from human pluripotent stem cells (hPSC-CMs) as an alternative source of human primary cardiomyocytes (CMs). In this study, remdesivir exhibited up to 60-fold higher Antiviral activity in hPSC-CMs compared to Vero E6 cells; however, it also induced moderate cardiotoxicity in these cells. To gain further insight into the drug-induced arrhythmogenic risk, we assessed QT interval prolongation and automaticity of remdesivir-treated hPSC-CMs using a multielectrode array (MEA). As a result, the data indicated a potential risk of QT prolongation when remdesivir is used at concentrations higher than the estimated peak plasma concentration. Therefore, we conclude that close monitoring of the electrocardiographic/QT interval should be advised in SARS-CoV-2-infected patients under remdesivir medication, in particular individuals with pre-existing heart conditions.

Keywords

COVID-19; Human cardiomyocytes; Pluripotent stem cells; Remdesivir; SARS-CoV-2.

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