Evidence mapPaperPMID 37422646Full record

ArticleVirology journal2023

Patch-clamp studies and cell viability assays suggest a distinct site for viroporin inhibitors on the E protein of SARS-CoV-2.

Ulrike Breitinger, Christine Adel Sedky, Heinrich Sticht, Hans-Georg Breitinger

Open access · goldAbstract read
In one paragraph

Article in Virology journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. The Redesign of the Molecular Scaffold of Viral Ion Channel Blockers.Computational and structural biotechnology journal · 2026
    Article
  2. Article
  3. Article
  4. Computational and structural biotechnology journal · 2025
    Article
  5. 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
  6. Article
  7. Review
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

4 authors at 2 institutions in 2 countries.

Ulrike BreitingerDepartment of Biochemistry, German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo, 11835, Egypt. ulrike.breitinger@guc.edu.eg.
Christine Adel SedkyDepartment of Biochemistry, German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo, 11835, Egypt.
Heinrich StichtDivision of Bioinformatics, Institute for Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Hans-Georg BreitingerDepartment of Biochemistry, German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo, 11835, Egypt.
German University in Cairo · EGFriedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSARS-CoV-2 has caused a worldwide pandemic since December 2019 and the search for pharmaceutical targets against COVID-19 remains an important challenge. Here, we studied the envelope protein E of SARS-CoV and SARS-CoV-2, a highly conserved 75-76 amino acid viroporin that is crucial for virus assembly and release. E protein channels were recombinantly expressed in HEK293 cells, a membrane-directing signal peptide ensured transfer to the plasma membrane.

methodsViroporin channel activity of both E proteins was investigated using patch-clamp electrophysiology in combination with a cell viability assay. We verified inhibition by classical viroporin inhibitors amantadine, rimantadine and 5-(N,N-hexamethylene)-amiloride, and tested four ivermectin derivatives.

resultsClassical inhibitors showed potent activity in patch-clamp recordings and viability assays. In contrast, ivermectin and milbemycin inhibited the E channel in patch-clamp recordings but displayed only moderate activity on the E protein in the cell viability assay, which is also sensitive to general cytotoxic activity of the tested compounds. Nemadectin and ivermectin aglycon were inactive. All ivermectin derivatives were cytotoxic at concentrations > 5 µM, i.e. below the level required for E protein inhibition.

conclusionsThis study demonstrates direct inhibition of the SARS-CoV-2 E protein by classical viroporin inhibitors. Ivermectin and milbemycin inhibit the E protein channel but their cytotoxicity argues against clinical application.

Indexed as

COVID-19Severe acute respiratory syndrome-related coronavirusCell SurvivalHEK293 CellsHumansIvermectinMacrolidesSARS-CoV-2Viroporin ProteinsIvermectinMacrolidesmoxidectinViroporin ProteinsCell viability assayE proteinIvermectin derivativesPatch-clamp electrophysiologySARS-CoV-2Viroporin inhibitorsViroporins

Identifiers

PMID37422646
PMCPMC10329798
OpenAlexW4383621428

What Socratic holds

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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 Socratic graph.