Evidence map›Paper›PMID 39412366›Full record

ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2024

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

Felix Wiedmann, Emika Boondej, Megan Stanifer, Amelie Paasche, Manuel Kraft, Merten Prüser, Timon Seeger, Ulrike Uhrig, Steeve Boulant, Constanze Schmidt

Abstract read
In one paragraph

Article in 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, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Addressing SARS-CoV-2 viroporins with antiarrhythmic drugs.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 · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Felix WiedmannDepartment of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.ORCID 0000-0001-8168-0025
Emika BoondejDepartment of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Megan StaniferDepartment of Molecular Genetics and Microbiology, University of Florida, College of Medicine, Gainesville, FL, USA.ORCID 0000-0002-5606-1297
Amelie PaascheDepartment of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.ORCID 0000-0001-6882-1428
Manuel KraftDepartment of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.ORCID 0000-0001-6764-2970
Merten PrüserDepartment of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Timon SeegerDepartment of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Ulrike UhrigChemical Biology Core Facility, EMBL, Heidelberg, Germany.ORCID 0000-0001-8799-2249
Steeve BoulantDepartment of Molecular Genetics and Microbiology, University of Florida, College of Medicine, Gainesville, FL, USA.ORCID 0000-0001-8614-4993
Constanze SchmidtDepartment of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.ORCID 0000-0001-5897-237X

Funding

Else-Kröner Fresenius FoundationGerman Cardiac SocietyGerman Centre for Cardiovascular ResearchGerman Foundation of Heart ResearchGerman Heart FoundationGerman Ministry of Education and ResearchGerman Research Foundation #422681845University of Florida
6 · The paper itself

Abstract

aimsCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to cardiovascular complications, notably cardiac arrhythmias. The open reading frame (ORF) 3a of the coronavirus genome encodes for a transmembrane protein that can function as an ion channel. The aim of this study was to investigate the role of the SARS-CoV-2 ORF 3a protein in COVID-19-associated arrhythmias and its potential as a pharmacological target. METHODS AND

resultsHuman-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and cultured human fibroblasts were infected with SARS-CoV-2. Subsequent immunoblotting assays revealed the expression of ORF 3a protein in hiPSC-CM but not in fibroblasts. After intracytoplasmic injection of RNA encoding ORF 3a proteins into Xenopus laevis oocytes, macroscopic outward currents could be measured. While class I, II, and IV antiarrhythmic drugs showed minor effects on ORF 3a-mediated currents, a robust inhibition was detected after application of class III antiarrhythmics. The strongest effects were observed with dofetilide and amiodarone. Finally, molecular docking simulations and mutagenesis studies identified key amino acid residues involved in drug binding.

conclusionClass III antiarrhythmic drugs are potential inhibitors of ORF 3a-mediated currents, offering new options for the treatment of COVID-19-related cardiac complications.

Indexed as

Anti-Arrhythmia AgentsMyocytes, CardiacSARS-CoV-2Xenopus laevisAnimalsArrhythmias, CardiacCells, CulturedCOVID-19COVID-19 Drug TreatmentFibroblastsHumansInduced Pluripotent Stem CellsMolecular Docking SimulationViral Envelope ProteinsViroporin Proteins3a protein, SARS-CoVAnti-Arrhythmia AgentsViral Envelope ProteinsViroporin Proteins3a proteinAntiarrhythmic drugsArrhythmiasCOVID

Identifiers

PMID39412366
PMCPMC11481279

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.