Evidence map›Paper›PMID 25155602›Full record

ArticleAntimicrobial agents and chemotherapy2014

Antiviral effects of artesunate on JC polyomavirus replication in COS-7 cells.

Biswa Nath Sharma, Manfred Marschall, Christine Hanssen Rinaldo

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
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  9. International journal of molecular sciences · 2020
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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

3 authors at 3 institutions in 2 countries.

Biswa Nath SharmaDepartment of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Manfred MarschallInstitute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany.
Christine Hanssen RinaldoDepartment of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway christine.rinaldo@unn.no.ORCID http://orcid.org/0000-0002-6970-6728
Friedrich-Alexander-Universität Erlangen-Nürnberg · DEUiT The Arctic University of Norway · NOUniversity Hospital of North Norway · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human JC polyomavirus (JCPyV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). A growing number of patients with induced or acquired immunosuppression are at risk for infection, and no effective antiviral therapy is presently available. The widely used antimalarial drug artesunate has shown broad antiviral activity in vitro but limited clinical success. The aim of this study was to investigate the effect of artesunate on JCPyV replication in vitro. The permissivity for JCPyV MAD-4 was first compared in four cell lines, and the monkey kidney cell line COS-7 was selected. Artesunate caused a concentration-dependent decrease in the extracellular JCPyV DNA load 96 h postinfection, with a 50% effective concentration (EC50) of 2.9 μM. This effect correlated with a decreased expression of capsid protein VP1 and a reduced release of infectious viral progeny. For concentrations of <20 μM, transient reductions in cellular DNA replication and proliferation were seen, while for higher concentrations, some cytotoxicity was detected. A selective index of 16.6 was found when cytotoxicity was calculated based on cellular DNA replication in the mock-infected cells, but interestingly, cellular DNA replication in the JCPyV-infected cells was more strongly affected. In conclusion, artesunate is efficacious in inhibiting JCPyV replication at micromolar concentrations, which are achievable in plasma. The inhibition at EC50 probably reflects an effect on cellular proteins and involves transient cytostatic effects. Our results, together with the favorable distribution of the active metabolite dihydroartemisinin to the central nervous system, suggest a potential use for artesunate in patients with PML.

Indexed as

AnimalsAntiviral AgentsArtemisininsArtesunateCell LineCell ProliferationCell SurvivalChlorocebus aethiopsCOS CellsDNA, ViralHEK293 CellsHumansJC VirusLeukoencephalopathy, Progressive MultifocalMicrobial Sensitivity TestsVirus ReplicationAntiviral AgentsArtemisininsArtesunateDNA, Viral

Identifiers

PMID25155602
PMCPMC4249435
OpenAlexW2033778630

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.