Evidence map›Paper›PMID 23620378›Full record

ArticleThe Journal of general virology2013

MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment.

Adriaan H de Wilde, V Stalin Raj, Diede Oudshoorn, Theo M Bestebroer, Stefan van Nieuwkoop, Ronald W A L Limpens, Clara C Posthuma, Yvonne van der Meer, Montserrat Bárcena, Bart L Haagmans and 2 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in The Journal of general virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04540926 (Utility of Low Doses of Corticosteroids and Cyclosporine Combined With Enoxaparin, in Patients With COVID-19 Pneumonia at the ISSSTE Regional Hospital, Puebla, During the Contingency Period Due to the SARS-Cov2 Pandemic), which is not on this map. Cited by 247 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
247citing papers in PubMed, 7 pooled it
17.2field-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.

NCT04540926 phase1 / phase2unknown statusnot on this mapstarted 2020, after this paper: background citation

Utility of Low Doses of Corticosteroids and Cyclosporine Combined With Enoxaparin, in Patients With COVID-19 Pneumonia at the ISSSTE Regional Hospital, Puebla, During the Contingency Period Due to the SARS-Cov2 Pandemic

TypeinterventionalSponsorInstituto de Seguridad y Servicios Sociales de los Trabajadores del EstadoRan2020 to 2020Enrolled200ConditionsCOVID 19 PneumoniaArmsCyclosporin A
3 · Its place in the literature

Who cites it

247 citing papers in PubMed, 7 syntheses or guidelines pooled it, 358 citations in OpenAlex.

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  16. Perturbation ofJournal of virology · 2025
    Article
  17. Anti-interferon armamentarium of human coronaviruses.Cellular and molecular life sciences : CMLS · 2025
    Review
  18. Advancements in the development of antivirals against SARS-Coronavirus.Frontiers in cellular and infection microbiology · 2025
    Review
  19. Article
  20. Article

187 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

12 authors at 3 institutions in 1 country.

Adriaan H de WildeMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
V Stalin RajViroscience Lab, Erasmus MC, Rotterdam, The Netherlands.
Diede OudshoornMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Theo M BestebroerViroscience Lab, Erasmus MC, Rotterdam, The Netherlands.
Stefan van NieuwkoopViroscience Lab, Erasmus MC, Rotterdam, The Netherlands.
Ronald W A L LimpensSection Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Clara C PosthumaMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Yvonne van der MeerMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Montserrat BárcenaSection Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Bart L HaagmansViroscience Lab, Erasmus MC, Rotterdam, The Netherlands.
Eric J SnijderMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Bernadette G van den HoogenViroscience Lab, Erasmus MC, Rotterdam, The Netherlands.
Leiden University Medical Center · NLErasmus University Rotterdam · NLErasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. The 2003 outbreak of severe acute respiratory syndrome (SARS) highlighted the potentially lethal consequences of CoV-induced disease in humans. In 2012, a novel CoV (Middle East Respiratory Syndrome coronavirus; MERS-CoV) emerged, causing 49 human cases thus far, of which 23 had a fatal outcome. In this study, we characterized MERS-CoV replication and cytotoxicity in human and monkey cell lines. Electron microscopy of infected Vero cells revealed extensive membrane rearrangements, including the formation of double-membrane vesicles and convoluted membranes, which have been implicated previously in the RNA synthesis of SARS-CoV and other CoVs. Following infection, we observed rapidly increasing viral RNA synthesis and release of high titres of infectious progeny, followed by a pronounced cytopathology. These characteristics were used to develop an assay for antiviral compound screening in 96-well format, which was used to identify cyclosporin A as an inhibitor of MERS-CoV replication in cell culture. Furthermore, MERS-CoV was found to be 50-100 times more sensitive to alpha interferon (IFN-α) treatment than SARS-CoV, an observation that may have important implications for the treatment of MERS-CoV-infected patients. MERS-CoV infection did not prevent the IFN-induced nuclear translocation of phosphorylated STAT1, in contrast to infection with SARS-CoV where this block inhibits the expression of antiviral genes. These findings highlight relevant differences between these distantly related zoonotic CoVs in terms of their interaction with and evasion of the cellular innate immune response.

Indexed as

Cytopathogenic Effect, ViralVirus ReplicationAnimalsAntiviral AgentsCell LineCell MembraneChlorocebus aethiopsCoronavirusCyclosporineDrug Evaluation, PreclinicalHumansInterferon-alphaMicrobial Sensitivity TestsMicroscopy, Electron, TransmissionAntiviral AgentsCyclosporineInterferon-alpha

Identifiers

PMID23620378
PMCPMC3749523
OpenAlexW2117336218

What OpenQuestion holds

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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.