Evidence map›Paper›PMID 27535052›Full record

ArticleJournal of virology2016

The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling.

Finny S Varghese, Bastian Thaa, Siti Naqiah Amrun, Diane Simarmata, Kai Rausalu, Tuula A Nyman, Andres Merits, Gerald M McInerney, Lisa F P Ng, Tero Ahola

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 2 pooled it
8.8field-weighted citation impact, top 2% 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

80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 148 citations in OpenAlex.

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20 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

10 authors at 5 institutions in 4 countries.

Finny S VargheseDepartment of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland finny.varghese@helsinki.fi tero.ahola@helsinki.fi.
Bastian ThaaDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Siti Naqiah AmrunSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
Diane SimarmataSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
Kai RausaluInstitute of Technology, University of Tartu, Tartu, Estonia.
Tuula A NymanInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.
Andres MeritsInstitute of Technology, University of Tartu, Tartu, Estonia.
Gerald M McInerneyDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Lisa F P NgSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
Tero AholaDepartment of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland finny.varghese@helsinki.fi tero.ahola@helsinki.fi.
University of Helsinki · FIAgency for Science, Technology and Research · SGKarolinska Institutet · SEUniversity of Tartu · EESingapore Immunology Network · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chikungunya virus (CHIKV) has infected millions of people in the tropical and subtropical regions since its reemergence in the last decade. We recently identified the nontoxic plant alkaloid berberine as an antiviral substance against CHIKV in a high-throughput screen. Here, we show that berberine is effective in multiple cell types against a variety of CHIKV strains, also at a high multiplicity of infection, consolidating the potential of berberine as an antiviral drug. We excluded any effect of this compound on virus entry or on the activity of the viral replicase. A human phosphokinase array revealed that CHIKV infection specifically activated the major mitogen-activated protein kinase (MAPK) signaling pathways extracellular signal-related kinase (ERK), p38 and c-Jun NH IMPORTANCE: Chikungunya virus (CHIKV) is a mosquito-borne virus that causes severe and persistent muscle and joint pain and has recently spread to the Americas. No licensed drug exists to counter this virus. In this study, we report that the alkaloid berberine is antiviral against different CHIKV strains and in multiple human cell lines. We demonstrate that berberine collectively reduced the virus-induced activation of cellular mitogen-activated protein kinase signaling. The relevance of these signaling cascades in the viral life cycle was emphasized by specific inhibitors of these kinase pathways, which decreased the production of progeny virions. Berberine significantly reduced CHIKV-induced inflammatory disease in a mouse model, demonstrating efficacy of the drug in vivo Overall, this work makes a strong case for pursuing berberine as a potential anti-CHIKV therapeutic compound and for exploring the MAPK signaling pathways as antiviral targets against alphavirus infections.

Indexed as

AlkaloidsAnimalsAntiviral AgentsBerberineCell LineChikungunya FeverChikungunya virusCricetinaeHEK293 CellsHumansJNK Mitogen-Activated Protein KinasesMiceMice, Inbred C57BLMitogen-Activated Protein KinasesPhosphorylationSignal TransductionAlkaloidsAntiviral AgentsBerberineJNK Mitogen-Activated Protein KinasesMitogen-Activated Protein Kinases

Identifiers

PMID27535052
PMCPMC5068526
OpenAlexW2512703240

What OpenQuestion holds

Textmetadata
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.