Key result
COVID-19 therapies including chloroquine and azithromycin may cause cardiotoxicity via hERG blockade and QT prolongation.
Why the study?
Potential therapeutic drugs for COVID-19 can cause cardiotoxicity and severe ventricular arrhythmias by blocking the hERG potassium channel, requiring a better understanding of drug-channel interactions to develop safer therapies.
Do potential COVID-19 therapeutic drugs cause QT interval prolongation and arrhythmias through hERG channel blockade?
Do potential COVID-19 therapeutic drugs cause QT interval prolongation and arrhythmias through hERG channel blockade?
Potential COVID-19 therapies like chloroquine and hydroxychloroquine carry a significant risk of QT prolongation and ventricular arrhythmias due to hERG channel blockade, requiring careful risk-benefit consideration.
Warrants QT monitoring with these agents; leaves open clinical arrhythmic risk magnitude in COVID-19.
The COVID-19 caused by SARS-CoV-2 poses a huge challenge to the medical system, especially the 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 attracting great attention. Clinically, however, many drugs including those currently shown to be effective against COVID-19 such as chloroquine, hydroxychloroquine, azithromycin and lopinavir/ritonavir may cause cardiotoxicity through acting on cardiac potassium channel, hERG channel due to their off-target effect. Blocking of hERG prolongs QT intervals on the electrocardiogram and thus 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 to cause arrhythmias can not be ignored. To develop safer and effective drugs, it is necessary to understand the interactions between drugs and hERG channels and the molecular mechanism behind this high affinity. In this review, we focus on the biochemical and molecular mechanistic aspects of related drug blockade in the hERG trying to provide insights into the QT interval prolongation caused by potential therapeutic drugs for COVID-19 and hope to weigh the risks and benefits when using related drugs.
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Zheng et al. (2020) conducted a review in COVID-19. COVID-19 drugs (chloroquine, hydroxychloroquine, azithromycin, lopinavir/ritonavir) was evaluated on QT interval prolongation and ventricular arrhythmias via hERG channel blockade. Potential COVID-19 therapies such as chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir may cause cardiotoxicity by blocking the hERG channel and prolonging the QT interval.
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