Evidence map›Paper›PMID 24874215›Full record

ArticlePLoS pathogens2014

Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus.

Anna Lundin, Ronald Dijkman, Tomas Bergström, Nina Kann, Beata Adamiak, Charles Hannoun, Eveline Kindler, Hulda R Jónsdóttir, Doreen Muth, Joeri Kint and 5 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04420260 (Scheme of Primary Prevention of Infection by COVID-19, in Workers), which is not on this map. Cited by 113 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 2 pooled it
6.5field-weighted citation impact, top 3% 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.

NCT04420260 nacompletednot on this mapstarted 2021, after this paper: background citation

Scheme of Primary Prevention of Infection by COVID-19, in Workers: Phase II Controlled Clinical Trial, to be Carried Out in Medellín-Antioquia

TypeinterventionalSponsorUnidad de Investigación Genética MolecularRan2021 to 2021Enrolled152ConditionsCOVIDArmsGroup A: oropharygeal spray and immunostimulant emulsion, Group D:Placebo oropharyngeal spray + Placebo taken PO
3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review

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

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

15 authors at 7 institutions in 4 countries.

Anna LundinDepartment of Clinical Virology, University of Gothenburg, Göteborg, Sweden.
Ronald DijkmanInstitute of Immunobiology, Kantonal Hospital St.Gallen, St.Gallen, Switzerland; Federal Department of Home Affairs, Institute of Virology and Immunology, Berne and Mittelhäusern, Switzerland.
Tomas BergströmDepartment of Clinical Virology, University of Gothenburg, Göteborg, Sweden.
Nina KannOrganic Chemistry, Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
Beata AdamiakDepartment of Clinical Virology, University of Gothenburg, Göteborg, Sweden.
Charles HannounDepartment of Clinical Virology, University of Gothenburg, Göteborg, Sweden.
Eveline KindlerInstitute of Immunobiology, Kantonal Hospital St.Gallen, St.Gallen, Switzerland; Federal Department of Home Affairs, Institute of Virology and Immunology, Berne and Mittelhäusern, Switzerland.
Hulda R JónsdóttirInstitute of Immunobiology, Kantonal Hospital St.Gallen, St.Gallen, Switzerland; Federal Department of Home Affairs, Institute of Virology and Immunology, Berne and Mittelhäusern, Switzerland.
Doreen MuthInstitute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Joeri KintDepartment of Animal Sciences, Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, Wageningen, The Netherlands; Merck Animal Health, Bioprocess Technology & Support, Boxmeer, The Netherlands.
Maria ForlenzaDepartment of Animal Sciences, Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
Marcel A MüllerInstitute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Christian DrostenInstitute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Volker ThielInstitute of Immunobiology, Kantonal Hospital St.Gallen, St.Gallen, Switzerland; Federal Department of Home Affairs, Institute of Virology and Immunology, Berne and Mittelhäusern, Switzerland; Vetsuisse Faculty, University of Berne, Berne, Switzerland.
Edward TrybalaDepartment of Clinical Virology, University of Gothenburg, Göteborg, Sweden.
University of Gothenburg · SEUniversity of Bonn · DEKantonsspital St. Gallen · CHWageningen University & Research · NLChalmers University of Technology · SEFederal Department of Home Affairs · CHUniversity of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.

Indexed as

CoronavirusRespiratory Syncytial VirusesAnimalsAntiviral AgentsCell LineCell MembraneCoronavirus InfectionsHumansRNA, ViralVirus InternalizationVirus ReplicationAntiviral AgentsRNA, Viral

Identifiers

PMID24874215
PMCPMC4038610
OpenAlexW2030550897

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.