Details

Autor(en) / Beteiligte

• Szendrey, Mark
• Guo, Jun
• Li, Wentao
• Yang, Tonghua
• Zhang, Shetuan

Titel

COVID-19 Drugs Chloroquine and Hydroxychloroquine, but Not Azithromycin and Remdesivir, Block hERG Potassium Channels

Ist Teil von

• The Journal of pharmacology and experimental therapeutics, 2021-05, Vol.377 (2), p.265

Ort / Verlag

United States

Erscheinungsjahr

2021

Link zum Volltext

Beschreibungen/Notizen

• Drug-induced long QT syndrome (LQTS) is an established cardiac side effect of a wide range of medications and represents a significant concern for drug safety. The rapidly and slowly activating delayed rectifier K currents, mediated by channels encoded by the human ether-a-go-go-related gene ( ) and KCNQ1 + KCNE1, respectively, are two main currents responsible for ventricular repolarization. The common cause for drugs to induce LQTS is through impairing the hERG channel. For the recent emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2, several drugs have been investigated as potential therapies; however, there are concerns about their QT prolongation risk. Here, we studied the effects of chloroquine, hydroxychloroquine, azithromycin, and remdesivir on hERG channels. Our results showed that although chloroquine acutely blocked hERG current (I ), with an IC of 3.0 µM, hydroxychloroquine acutely blocked I 8-fold less potently, with an IC of 23.4 µM. Azithromycin and remdesivir did not acutely affect I When these drugs were added at 10 µM to the cell culture medium for 24 hours, remdesivir increased I by 2-fold, which was associated with an increased mature hERG channel expression. In addition, these four drugs did not acutely or chronically affect KCNQ1 + KCNE1 channels. Our data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns. SIGNIFICANCE STATEMENT: This work demonstrates that, among off-label potential COVID-19 treatment drugs chloroquine, hydroxychloroquine, azithromycin, and remdesivir, the former two drugs block hERG potassium channels, whereas the latter two drugs do not. All four drugs do not affect KCNQ1 + KCNE1. As hERG and KCNQ1 + KCNE1 are two main K channels responsible for ventricular repolarization, and most drugs that induce long QT syndrome (LQTS) do so by impairing hERG channels, these data provide insight into COVID-19 drug-associated LQTS and cardiac safety concerns.