1. Off-label use of chloroquine, hydroxychloroquine, azithromycin and lopinavir/ritonavir in COVID-19 risks prolonging the QT interval by targeting the hERG channel.
- Author
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Zequn Z, Yujia W, Dingding Q, and Jiangfang L
- Subjects
- Drug Combinations, Humans, Long QT Syndrome epidemiology, Off-Label Use, Azithromycin adverse effects, Azithromycin therapeutic use, COVID-19 complications, Chloroquine adverse effects, Chloroquine therapeutic use, ERG1 Potassium Channel drug effects, Hydroxychloroquine adverse effects, Hydroxychloroquine therapeutic use, Long QT Syndrome chemically induced, Lopinavir adverse effects, Lopinavir therapeutic use, Ritonavir adverse effects, Ritonavir therapeutic use, COVID-19 Drug Treatment
- Abstract
Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an enormous challenge to the medical system, especially the lack of safe and effective COVID-19 treatment methods, forcing people to look for drugs that may have therapeutic effects as soon as possible. Some old drugs have shown clinical benefits after a few small clinical trials that attracted great attention. Clinically, however, many drugs, including those currently used in COVID-19, such as chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir, may cause cardiotoxicity by acting on cardiac potassium channels, especially hERG channel through their off-target effects. The blocking of the hERG channel prolongs QT intervals on electrocardiograms; thus, it might induce severe ventricular arrhythmias and even sudden cardiac death. Therefore, while focusing on the efficacy of COVID-19 drugs, the fact that they block hERG channels to cause arrhythmias cannot be ignored. To develop safer and more effective drugs, it is necessary to understand the interactions between drugs and the hERG channel and the molecular mechanism behind this high affinity. In this review, we focus on the biochemical and molecular mechanistic aspects of drug-related blockade of the hERG channel to provide insights into QT prolongation caused by off-label use of related drugs in COVID-19, and hope to weigh the risks and benefits when using these drugs., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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