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.
【저자키워드】 COVID-19, Remdesivir, SARS-CoV-2., pluripotent stem cells, Human cardiomyocytes, 【초록키워드】 coronavirus disease, stem cells, SARS-CoV-2, Coronavirus disease 2019, Human, drugs, Remdesivir, risk, antiviral activity, severe acute respiratory syndrome Coronavirus, Emergency use authorization, Health crisis, QT prolongation, Severe acute respiratory syndrome, pluripotent stem cells, VERO E6 cells, respiratory, medication, information, QT interval, moderate, safety profile, Coronavirus-2, Concentration, Emergency, Cardiotoxicity, Vero E6, therapeutic option, acute respiratory syndrome, peak plasma concentration, acute respiratory syndrome coronavirus, global public health, These cells, individual, potential risk, acute respiratory syndrome coronavirus-2, SARS-CoV-2-infected patients, drug candidate, authorization, close monitoring, pluripotent stem cell, automaticity, caused, indicated, evaluated, exhibited, suggested, conditions, multielectrode, SARS-CoV-2-infected patient, 【제목키워드】 SARS-COV-2 infection, Remdesivir,