Potential therapeutic drugs for COVID-19 risk prolonging QT interval
targeting hERG channel
Abstract
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.