Related Experiment Video

Updated: Jun 10, 2025

High-Throughput Optical Controlling and Recording Calcium Signal in iPSC-Derived Cardiomyocytes for Toxicity Testing and Phenotypic Drug Screening
10:01

High-Throughput Optical Controlling and Recording Calcium Signal in iPSC-Derived Cardiomyocytes for Toxicity Testing and Phenotypic Drug Screening

Published on: March 31, 2022

3.1K

SARS-CoV-2 ORF 3a-mediated currents are inhibited by antiarrhythmic drugs

Felix Wiedmann1,2,3, Emika Boondej1, Megan Stanifer4

  • 1Department of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.

Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology
|October 16, 2024
PubMed

Insights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) open reading frame 3a protein contributes to COVID-19 cardiac arrhythmias. Class III antiarrhythmics, like dofetilide and amiodarone, effectively inhibit these effects, offering new therapeutic avenues.

Area of Science:

  • Cardiology
  • Virology
  • Molecular Biology

Background:

  • COVID-19, caused by SARS-CoV-2, is associated with cardiac arrhythmias.
  • The SARS-CoV-2 ORF 3a protein, a transmembrane ion channel, is implicated in these cardiovascular complications.

Purpose of the Study:

  • To investigate the role of SARS-CoV-2 ORF 3a protein in COVID-19-associated arrhythmias.
  • To evaluate ORF 3a as a potential pharmacological target for treating cardiac complications.

Main Methods:

  • Infection of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and fibroblasts with SARS-CoV-2.
  • Expression analysis of ORF 3a protein using immunoblotting.
  • Electrophysiological studies in Xenopus laevis oocytes after ORF 3a injection.
  • Drug screening with various antiarrhythmic classes and molecular docking simulations.

Main Results:

  • ORF 3a protein was expressed in hiPSC-CM but not fibroblasts.
  • ORF 3a induced measurable ion currents in oocytes.
  • Class III antiarrhythmics, particularly dofetilide and amiodarone, robustly inhibited ORF 3a-mediated currents.
  • Key amino acid residues involved in drug binding were identified.

Conclusions:

  • SARS-CoV-2 ORF 3a protein contributes to cardiac arrhythmias.
  • Class III antiarrhythmic drugs show potential for treating COVID-19-related cardiac complications by inhibiting ORF 3a activity.
Abstract

Keywords:
3a proteinAntiarrhythmic drugsArrhythmiasCOVID

More Related Videos

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-208:41

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2

Published on: November 5, 2021

2.7K
Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents10:53

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

20.4K

Related Concept Videos

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
918
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
1.3K
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which...
716
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers01:20

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
788
Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
534
Antianginal Drugs: Calcium Channel Blockers and Ranolazine01:25

Antianginal Drugs: Calcium Channel Blockers and Ranolazine

Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
462