Evidence map›Paper›PMID 42697841›Full record

ArticleVirulence2026

Dual HBV cccDNA-linked HiBiT reporter hepatocyte models for screening of candidate cccDNA modulators.

Jiali Cao, Yali Zhang, Jian Ma, Shaojuan Wang, Yangtao Wu, Hualong Xiong, Mingfeng Wang, Tianshu Shi, Baorong Fu, Xiaochun Fu and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Virulence, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

14 authors.

Jiali CaoDepartment of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.ORCID 0000-0002-6286-5574
Yali ZhangState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
Jian MaState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
Shaojuan WangState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
Yangtao WuState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
Hualong XiongState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
Mingfeng WangState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
Tianshu ShiState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
Baorong FuState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
Xiaochun FuDepartment of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.
Xiaoli ChenDepartment of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.
Huiming YeDepartment of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.ORCID 0000-0003-2069-3644
Ningshao XiaState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
Quan YuanState Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic hepatitis B remains difficult to cure because the viral covalently closed circular DNA (cccDNA) minichromosome can persist and sustain viral transcription, creating a need for scalable, reporter readouts that facilitate early discovery of cccDNA-modulating agents. Here, we developed two complementary hepatocyte HiBiT reporter models: a replication-competent HBV reporter in HepaRG cells (HepaRG-Hibit16), in which a secreted split-NanoLuc HiBiT signal is linked to cccDNA-associated expression, and a Cre/Lox-based recombinant cccDNA (rcccDNA) reporter in HepG2 cells (HepG2-Rccc1a) that rapidly generates rcccDNA with a matched HiBiT readout. Screening of 1,403 FDA-approved compounds across both models identified 13 concordant, non-cytotoxic hits. Palovarotene, a retinoic acid receptor-γ agonist, was selected as an exemplar concordant hit and reduced HBV antigens, HBV DNA, and cccDNA and inhibited HBV infection in multiple hepatocyte-based

Indexed as

Antiviral AgentsDNA, CircularDNA, ViralHepatitis B virusHepatocytesDrug Evaluation, PreclinicalGenes, ReporterHep G2 CellsHumansVirus ReplicationAntiviral AgentsDNA, CircularDNA, Viralantiviral effectcccDNAHepatitis B viruspaired screeningreporter model

Identifiers

PMID42697841
PMCPMC13556949

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Registered trials

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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.