Evidence map›Paper›PMID 30779774›Full record

ArticlePloS one2019

Screening for inhibitor of episomal DNA identified dicumarol as a hepatitis B virus inhibitor.

Fumihiko Takeuchi, Sotaro Ikeda, Yuta Tsukamoto, Yoshikazu Iwasawa, Chen Qihao, Yukie Otakaki, Ouda Ryota, Wan-Ling Yao, Ryo Narita, Hijikata Makoto and 7 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

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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

17 authors at 7 institutions in 3 countries.

Fumihiko TakeuchiGraduate School of Biostudies, Kyoto University, Kyoto, Japan.
Sotaro IkedaGraduate School of Biostudies, Kyoto University, Kyoto, Japan.
Yuta TsukamotoDepartment of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Yoshikazu IwasawaGraduate School of Biostudies, Kyoto University, Kyoto, Japan.
Chen QihaoGraduate School of Biostudies, Kyoto University, Kyoto, Japan.
Yukie OtakakiGraduate School of Biostudies, Kyoto University, Kyoto, Japan.
Ouda RyotaDepartment of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Wan-Ling YaoGraduate School of Biostudies, Kyoto University, Kyoto, Japan.
Ryo NaritaDepartment of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Hijikata MakotoGraduate School of Biostudies, Kyoto University, Kyoto, Japan.
Koichi WatashiDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Takaji WakitaDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Koh TakeuchiMolecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan.ORCID 0000-0002-6227-4627
Kazuaki ChayamaLiver Research Project Center, Hiroshima University, Hiroshima, Japan.
Amane KogureDepartment of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Hiroki KatoGraduate School of Biostudies, Kyoto University, Kyoto, Japan.
Takashi FujitaGraduate School of Biostudies, Kyoto University, Kyoto, Japan.ORCID 0000-0001-9961-0535
Kyoto University · JPAarhus University · DKHiroshima University · JPHokkaido University · JPNational Institute of Advanced Industrial Science and Technology · JPNational Institute of Infectious Diseases · JPTokyo University of Science · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Currently, there is no available therapy to eradicate hepatitis B virus (HBV) in chronically infected individuals. This is due to the difficulty in eliminating viral covalently closed circular (ccc) DNA, which is central to the gene expression and replication of HBV. We developed an assay system for nuclear circular DNA using an integration-deficient lentiviral vector. This vector produced non-integrated circular DNA in nuclei of infected cells. We engineered this vector to encode firefly luciferase to monitor the lentiviral episome DNA. We screened 3,840 chemicals by this assay for luciferase-reducing activity and identified dicumarol, which is known to have anticoagulation activity. We confirmed that dicumarol reduced lentiviral episome DNA. Furthermore, dicumarol inhibited HBV replication in cell culture using NTCP-expressing HepG2 and primary human hepatocytes. Dicumarol reduced intracellular HBV RNA, DNA, supernatant HBV antigens and DNA. We also found that dicumarol reduced the cccDNA level in HBV infected cells, but did not affect HBV adsorption/entry. This is a novel assay system for screening inhibitors targeting nuclear cccDNA and is useful for finding new antiviral substances for HBV.

Indexed as

Antiviral AgentsCell NucleusDicumarolDNA, ViralDrug Evaluation, PreclinicalGenetic VectorsHEK293 CellsHepatitis B virusHep G2 CellsHumansLentivirusPlasmidsRNA, ViralAntiviral AgentsDicumarolDNA, ViralRNA, Viral

Identifiers

PMID30779774
PMCPMC6380541
OpenAlexW2915111751

What OpenQuestion holds

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LicenceCC BY
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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.