Evidence map›Paper›PMID 34222850›Full record

ArticleJHEP reports : innovation in hepatology2021

A new high-content screening assay of the entire hepatitis B virus life cycle identifies novel antivirals.

Jaewon Yang, Alexander König, Soonju Park, Eunji Jo, Pil Soo Sung, Seung Kew Yoon, Eva Zusinaite, Denis Kainov, David Shum, Marc Peter Windisch

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PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2021. 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
–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

7 citing papers in PubMed.

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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

10 authors.

Jaewon YangApplied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si, South Korea.
Alexander KönigApplied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si, South Korea.
Soonju ParkScreening Discovery Platform, Institut Pasteur Korea, Seongnam-si, South Korea.
Eunji JoApplied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si, South Korea.
Pil Soo SungDivision of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Seung Kew YoonDivision of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Eva ZusinaiteInstitute of Technology, University of Tartu, Tartu, Estonia.
Denis KainovInstitute of Technology, University of Tartu, Tartu, Estonia.
David ShumScreening Discovery Platform, Institut Pasteur Korea, Seongnam-si, South Korea.
Marc Peter WindischApplied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si, South Korea.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsChronic hepatitis B is an incurable disease. Addressing the unmet medical need for therapies has been hampered by a lack of suitable cell culture models to investigate the HBV life cycle in a single experimental setup. We sought to develop a platform suitable to investigate all aspects of the entire HBV life cycle.

methodsHepG2-NTCPsec+ cells were inoculated with HBV. Supernatants of infected cells were transferred to naïve cells. Inhibition of infection was determined in primary and secondary infected cells by high-content imaging of viral and cellular factors. Novel antivirals were triaged in cells infected with cell culture- or patient-derived HBV and in stably virus replicating cells. HBV internalisation and target-based receptor binding assays were conducted.

resultsWe developed an HBV platform, screened 2,102 drugs and bioactives, and identified 3 early and 38 late novel HBV life cycle inhibitors using infectious HBV genotype D. Two early inhibitors, pranlukast (EC

conclusionsThe newly developed high-content assay is suitable to screen large-scale drug libraries, enables monitoring of the entire HBV life cycle, and discriminates between inhibition of early and late viral life cycle events. LAY SUMMARY: HBV infection is an incurable, chronic disease with few available treatments. Addressing this unmet medical need has been hampered by a lack of suitable cell culture models to study the entire viral life cycle in a single experimental setup. We developed an image-based approach suitable to screen large numbers of drugs, using a cell line that can be infected by HBV and produces large amounts of virus particles. By transferring viral supernatants from these infected cells to uninfected target cells, we could monitor the entire viral life cycle. We used this system to screen drug libraries and identified novel anti-HBV inhibitors that potently inhibit HBV in various phases of its life cycle. This assay will be an important new tool to study the HBV life cycle and accelerate the development of novel therapeutic strategies.

Indexed as

CC50, 50% cytotoxic concentrationcccDNA, covalently closed circular DNACHB, chronic hepatitis BCpAM, core protein allosteric modifiers%CV, percent coefficient of variationdpi, days post-infectionDRC, dose–response curveEntryFDA-approved drugsFDA, Food and Drug AdministrationGEq, genome equivalentsHBVHBVpt, patient-derived HBVHCC, hepatocellular carcinomaHCS, high content screeningHepG2-NTCPHID, N-hydroxyisoquinolinedioneHigh-throughput screeningHLCs, hepatocyte-like cellsHTS, high-throughput screeningIFA, immunofluorescence analysisIFNα, interferon alphaIFNλ, interferon lambda%Imax, percent maximum inhibitioniPSCs, induced pluripotent stem cellsLHB, HBV large surface proteinLMV, lamivudineMoA, mechanism of actionMyrB, myrcludex BNTCP, sodium taurocholate cotransporting polypeptidep1, passage 1p2, passage 2Patient-derived HBVPEG, polyethylene glycolPF-rcDNA, protein-free relaxed circular DNApgRNA, pregenomic RNAReplicationSARS-CoV-2, severe acute respiratory syndrome coronavirus 2Small-molecule inhibitorsSOP, standard operation procedureSupernatant transferTDF, tenofovir disoproxil fumarateTI, therapeutic indexVirion secretion

Identifiers

PMID34222850
PMCPMC8243515

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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.