Evidence map›Paper›PMID 26856848›Full record

ArticleAntimicrobial agents and chemotherapy2016

Screening of a Library of FDA-Approved Drugs Identifies Several Enterovirus Replication Inhibitors That Target Viral Protein 2C.

Rachel Ulferts, S Matthijn de Boer, Lonneke van der Linden, Lisa Bauer, Hey Rhyoung Lyoo, Maria J Maté, Julie Lichière, Bruno Canard, Daphne Lelieveld, Wienand Omta and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 76 citations in OpenAlex.

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  16. Enterovirus A71 antivirals: Past, present, and future.Acta pharmaceutica Sinica. B · 2022
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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

13 authors at 6 institutions in 2 countries.

Rachel UlfertsDepartment of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
S Matthijn de BoerDepartment of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Lonneke van der LindenDepartment of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands.
Lisa BauerDepartment of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Hey Rhyoung LyooDepartment of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Maria J MatéCNRS, AFMB UMR 7257, Marseille, France Aix-Marseille Université, CNRS, AFMB UMR 7257, Marseille, France.
Julie LichièreCNRS, AFMB UMR 7257, Marseille, France Aix-Marseille Université, CNRS, AFMB UMR 7257, Marseille, France.
Bruno CanardCNRS, AFMB UMR 7257, Marseille, France Aix-Marseille Université, CNRS, AFMB UMR 7257, Marseille, France.
Daphne LelieveldCell Screening Core, Department of Cell Biology, Center for Molecular Medicine, UMC Utrecht, Utrecht, The Netherlands.
Wienand OmtaCell Screening Core, Department of Cell Biology, Center for Molecular Medicine, UMC Utrecht, Utrecht, The Netherlands.
David EganCell Screening Core, Department of Cell Biology, Center for Molecular Medicine, UMC Utrecht, Utrecht, The Netherlands.
Bruno CoutardCNRS, AFMB UMR 7257, Marseille, France Aix-Marseille Université, CNRS, AFMB UMR 7257, Marseille, France.
Frank J M van KuppeveldDepartment of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands F.J.M.vanKuppeveld@uu.nl.
Utrecht University · NLAix-Marseille Université · FRUniversity Medical Center Utrecht · NLAcademic Medical Center · NLArchitecture et Fonction des Macromolécules Biologiques · FRCentre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Enteroviruses (EVs) represent many important pathogens of humans. Unfortunately, no antiviral compounds currently exist to treat infections with these viruses. We screened the Prestwick Chemical Library, a library of approved drugs, for inhibitors of coxsackievirus B3, identified pirlindole as a potent novel inhibitor, and confirmed the inhibitory action of dibucaine, zuclopenthixol, fluoxetine, and formoterol. Upon testing of viruses of several EV species, we found that dibucaine and pirlindole inhibited EV-B and EV-D and that dibucaine also inhibited EV-A, but none of them inhibited EV-C or rhinoviruses (RVs). In contrast, formoterol inhibited all enteroviruses and rhinoviruses tested. All compounds acted through the inhibition of genome replication. Mutations in the coding sequence of the coxsackievirus B3 (CV-B3) 2C protein conferred resistance to dibucaine, pirlindole, and zuclopenthixol but not formoterol, suggesting that 2C is the target for this set of compounds. Importantly, dibucaine bound to CV-B3 protein 2C in vitro, whereas binding to a 2C protein carrying the resistance mutations was reduced, providing an explanation for how resistance is acquired.

Indexed as

Antiviral AgentsCarbazolesCarrier ProteinsClopenthixolDibucaineEnterovirusFluoxetineFormoterol FumarateHeLa CellsHumansRhinovirusViral Nonstructural ProteinsViral ProteinsVirus Replication2C protein, viralAntiviral AgentsCarbazolesCarrier ProteinsClopenthixolDibucaineFluoxetineFormoterol FumaratepirlindoleViral Nonstructural ProteinsViral Proteins

Identifiers

PMID26856848
PMCPMC4862474
OpenAlexW2337034576

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.