Therapeutic measures for COVID-19 and their clinical relevance of hERG channel translocation: A Pharmacodynamic approach

The COVID-19 caused by SARS-CoV-2 poses a massive 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 significant attention. Clinically, however, many medications, including those currently shown to be effective against COVID-19, such as Chloroquine, hydroxychloroquine, azithromycin and lopinavir/ritonavir, may cause cardiotoxicity by 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 from causing arrhythmias cannot be ignored. To develop safe 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.