Evidence map›Paper›PMID 30768944›Full record

ArticleAntiviral research2019

Inhibition of HBV replication by N-hydroxyisoquinolinedione and N-hydroxypyridinedione ribonuclease H inhibitors.

Tiffany C Edwards, Nagraj Mani, Bruce Dorsey, Ramesh Kakarla, Rene Rijnbrand, Michael J Sofia, John E Tavis

Open access · greenAbstract read
In one paragraph

Article in Antiviral research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Discovery ofInternational journal of molecular sciences · 2025
    Article
  3. Article
  4. Article
  5. Efficacy andAntimicrobial agents and chemotherapy · 2025
    Article
  6. Molecules (Basel, Switzerland) · 2024
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Recent Advances in Hepatitis B Treatment.Pharmaceuticals (Basel, Switzerland) · 2021
    Review
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

7 authors at 3 institutions in 3 countries.

Tiffany C EdwardsDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA; Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO, USA. Electronic address: Tiffany.Edwards@slu.edu.
Nagraj ManiArbutus Biopharma Incorporated, Warminster, PA, USA. Electronic address: nmani@arbutusbio.com.
Bruce DorseyArbutus Biopharma Incorporated, Warminster, PA, USA. Electronic address: bdorsey@arbutusbio.com.
Ramesh KakarlaArbutus Biopharma Incorporated, Warminster, PA, USA. Electronic address: rkakarla@arbutusbio.com.
Rene RijnbrandArbutus Biopharma Incorporated, Warminster, PA, USA. Electronic address: rrijnbrand@arbutusbio.com.
Michael J SofiaArbutus Biopharma Incorporated, Warminster, PA, USA. Electronic address: msofia@arbutsbio.com.
John E TavisDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA; Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO, USA. Electronic address: John.Tavis@health.slu.edu.
Arbutus Biopharma (Canada) · CASaint Louis University · ESSaint Louis University · US

Funding

Defining approaches for improving HID and HPD compounds as HBV RNaseH antagonistsR21AI124672 · NIAID · SAINT LOUIS UNIVERSITY · PI MEYERS, MARVIN J, TAVIS, JOHN E · 2017 to 2018
$417k
NIAID NIH HHS R21 AI124672
6 · The paper itself

Abstract

We recently developed a screening system capable of identifying and evaluating inhibitors of the Hepatitis B virus (HBV) ribonuclease H (RNaseH), which is the only HBV enzyme not targeted by current anti-HBV therapies. Inhibiting the HBV RNaseH blocks synthesis of the positive-polarity DNA strand, causing early termination of negative-polarity DNA synthesis and accumulation of RNA:DNA heteroduplexes. We previously reported inhibition of HBV replication by N-hydroxyisoquinolinediones (HID) and N-hydroxypyridinediones (HPD) in human hepatoma cells. Here, we report results from our ongoing efforts to develop more potent anti-HBV RNaseH inhibitors in the HID/HPD compound classes. We synthesized and screened additional HIDs and HPDs for preferential suppression of positive-polarity DNA in cells replicating HBV. Three of seven new HIDs inhibited HBV replication, however, the therapeutic indexes (TI = CC

Indexed as

Antiviral AgentsDNA ReplicationHepatitis B virusHumansIsoquinolinesPyridinesPyridonesRibonuclease HViral ProteinsVirus ReplicationAntiviral AgentshydroxypyridinesIsoquinolinesN-hydroxyisoquinolinedioneN-hydroxypyridinedionePyridinesPyridonesRibonuclease HViral ProteinsAntiviralHBVN-hydroxyisoquinolinedionesN-hydroxypyridinedionesRibonuclease HStructure-activity relationship

Identifiers

PMID30768944
PMCPMC10587990
OpenAlexW2912166467

What OpenQuestion holds

Textmetadata
LicenceTDM
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.