Journal
ANTIVIRAL RESEARCH
Volume 184, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.antiviral.2020.104955
Keywords
COVID-19; SARS-CoV-2; Human cardiomyocytes; Pluripotent stem cells; Remdesivir
Categories
Funding
- Ministry of Health and Welfare, Republic of Korea [HI20C0184]
- Ministry of Trade, Industry & Energy, Republic of Korea [20009748]
- Korea Centers for Disease Control and Prevention [2020-ER6106-00]
- Ministry of Science and ICT (National Research Foundation of Korea, Republic of Korea) [NRF-2020M3A9I2081687]
- KRICT intramural funding, Republic of Korea [KK-2032-20]
- City University of Hong Kong, Hong Kong SAR, China
- Korea Evaluation Institute of Industrial Technology (KEIT) [20009748] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Korea Health Promotion Institute [2020-ER6106-00, HI20C0184020020] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2020M3A9I2081687] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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