Evidence map›Paper›PMID 29789363›Full record

ArticlemBio2018

Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis.

Carlos Castaño-Rodriguez, Jose M Honrubia, Javier Gutiérrez-Álvarez, Marta L DeDiego, Jose L Nieto-Torres, Jose M Jimenez-Guardeño, Jose A Regla-Nava, Raul Fernandez-Delgado, Carmina Verdia-Báguena, Maria Queralt-Martín and 5 more

Erratum issued Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in mBio, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04894617 (Amantadine for COVID-19), which is not on this map. Cited by 198 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
198citing papers in PubMed, 2 pooled it
26.6field-weighted citation impact, top 1% 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.

NCT04894617 phase3unknown statusnot on this mapstarted 2021, after this paper: background citation

Amantadine for COVID-19: A Randomized, Placebo Controlled, Double-blinded, Clinical Trial

TypeinterventionalSponsorCopenhagen University Hospital, HvidovreRan2021 to 2022Enrolled226ConditionsCovid19ArmsAmantadine, Lactose monohydrate
3 · Its place in the literature

Who cites it

198 citing papers in PubMed, 2 syntheses or guidelines pooled it, 325 citations in OpenAlex.

  1. Pooled it
  2. Colchicine for the treatment of COVID-19.The Cochrane database of systematic reviews · 2021
    Pooled it
  3. Trial
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  7. Article
  8. SARS-CoV-2-derived RNA replicons as safe and effective vaccines.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Effects ofiMetaOmics · 2025
    Article
  10. Article
  11. Article
  12. Nonlytic Egress and Transmission in the Virus World.Annual review of biochemistry · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. SARS-CoV-2 ORF 3a-mediated currents are inhibited by 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
  20. Article

138 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

Carlos Castaño-RodriguezDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Jose M HonrubiaDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Javier Gutiérrez-ÁlvarezDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Marta L DeDiegoDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Jose L Nieto-TorresDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Jose M Jimenez-GuardeñoDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Jose A Regla-NavaDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Raul Fernandez-DelgadoDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Carmina Verdia-BáguenaDepartment of Physics, Laboratory of Molecular Biophysics, Universitat Jaume I, Castelló, Spain.
Maria Queralt-MartínEunice Kennedy Shriver NICHD, NIH, Bethesda, Maryland, USA.
Grazyna KochanImmunomodulation Group, Navarrabiomed-Biomedical Research Centre, IdISNA, Pamplona, Navarra, Spain.
Stanley PerlmanDepartment of Microbiology, University of Iowa, Iowa City, Iowa, USA.ORCID 0000-0003-4213-2354
Vicente M AguilellaDepartment of Physics, Laboratory of Molecular Biophysics, Universitat Jaume I, Castelló, Spain.
Isabel SolaDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Luis EnjuanesDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain L.Enjuanes@cnb.csic.es.
Centro Nacional de Biotecnología · ESUniversitat Jaume I · ESNavarrabiomed · ESUniversity of Iowa · US

Funding

SARS-CoV Proteins in Heterologous Viral InfectionP01AI060699 · NIAID · UNIVERSITY OF IOWA · PI PERLMAN, STANLEY · 2004 to 2021
$21.5M
Role of eicosanoids in pathogenic human CoV infectionsR01AI129269 · NIAID · UNIVERSITY OF IOWA · PI Stanley Perlman · 2016 to 2026
$4.7M
NIAID NIH HHS HHSN266200700010CNIAID NIH HHS P01 AI060699NIAID NIH HHS R01 AI129269
6 · The paper itself

Abstract

Viroporins are viral proteins with ion channel (IC) activity that play an important role in several processes, including virus replication and pathogenesis. While many coronaviruses (CoVs) encode two viroporins, severe acute respiratory syndrome CoV (SARS-CoV) encodes three: proteins 3a, E, and 8a. Additionally, proteins 3a and E have a PDZ-binding motif (PBM), which can potentially bind over 400 cellular proteins which contain a PDZ domain, making them potentially important for the control of cell function. In the present work, a comparative study of the functional motifs included within the SARS-CoV viroporins was performed, mostly focusing on the roles of the IC and PBM of E and 3a proteins. Our results showed that the full-length E and 3a proteins were required for maximal SARS-CoV replication and virulence, whereas viroporin 8a had only a minor impact on these activities. A virus missing both the E and 3a proteins was not viable, whereas the presence of either protein with a functional PBM restored virus viability. E protein IC activity and the presence of its PBM were necessary for virulence in mice. In contrast, the presence or absence of the homologous motifs in protein 3a did not influence virus pathogenicity. Therefore, dominance of the IC and PBM of protein E over those of protein 3a was demonstrated in the induction of pathogenesis in mice.

Indexed as

Virus ReplicationAnimalsChlorocebus aethiopsFemaleHumansMiceMice, Inbred BALB CSevere Acute Respiratory SyndromeSevere acute respiratory syndrome-related coronavirusVero CellsViral Envelope ProteinsViral ProteinsViroporin ProteinsVirulence3a protein, SARS-CoVE protein, SARS coronavirusViral Envelope ProteinsViral ProteinsViroporin ProteinscoronavirusPBMPDZSARS-CoVviroporins

Identifiers

PMID29789363
PMCPMC5964350
OpenAlexW2803294153

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Read underepoch 390

Registered trials

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.