favipiravir and Heart-Diseases

After the outbreak of COVID-19, many novel drugs have been introduced to improve patients' conditions. Remdesivir and Favipiravir are among the most common drugs used against SARS-CoV-2. Although promising, cardiovascular side effects of these drugs should be considered by physicians and nurses. In this study, we searched databases for assessing the cardiovascular side effects of Remdesivir and Favipiravir. It seems that despite the beneficial effects of these drugs, due to the cardiovascular complications of COVID-19 and cardiovascular side effects of these drugs, which can overlap with each other, the use of these drugs can be a challenging issue in the cardiovascular practice.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; COVID-19 Drug Treatment; Heart Diseases; Humans; Pyrazines; SARS-CoV-2

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.

Topics: Adenosine Monophosphate; Alanine; Amides; Animals; Antimalarials; Antiviral Agents; Chlorocebus aethiops; Chloroquine; COVID-19; COVID-19 Drug Treatment; Electrocardiography; Flow Cytometry; Heart Diseases; Humans; Hydroxychloroquine; Microscopy, Fluorescence; Myocytes, Cardiac; Pluripotent Stem Cells; Pyrazines; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Vero Cells; Viral Plaque Assay