Evidence map›Paper›PMID 22740655›Full record

ArticleNucleic acids research2012

Identification and analysis of hepatitis C virus NS3 helicase inhibitors using nucleic acid binding assays.

Sourav Mukherjee, Alicia M Hanson, William R Shadrick, Jean Ndjomou, Noreena L Sweeney, John J Hernandez, Diana Bartczak, Kelin Li, Kevin J Frankowski, Julie A Heck and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

38 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Identifying RNA Helicase Inhibitors Using Duplex Unwinding Assays.Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  9. Inhibition of Orbivirus Replication by Aurintricarboxylic Acid.International journal of molecular sciences · 2020
    Article
  10. Article
  11. 100 Years of Suramin.Antimicrobial agents and chemotherapy · 2020
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Therapeutic Approaches for Zika Virus Infection of the Nervous System.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017
    Review
  18. Article
  19. Article
  20. 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

13 authors at 2 institutions in 1 country.

Sourav MukherjeeDepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
Alicia M Hanson
William R Shadrick
Jean Ndjomou
Noreena L Sweeney
John J Hernandez
Diana Bartczak
Kelin Li
Kevin J Frankowski
Julie A Heck
Leggy A Arnold
Frank J Schoenen
David N Frick
New York Medical College · USUniversity of Wisconsin–Milwaukee · US

Funding

University of Kansas Specialized Chemistry CenterU54HG005031 · NHGRI · UNIVERSITY OF KANSAS LAWRENCE · PI AUBE, JEFFREY · 2008 to 2013
$21.5M
Antiviral potential of helicase inhibitorsR01AI088001 · NIAID · UNIVERSITY OF WISCONSIN MILWAUKEE · PI FRICK, DAVID N · 2010 to 2012
$1.1M
NHGRI NIH HHS U54 HG005031NIAID NIH HHS R01 AI088001
6 · The paper itself

Abstract

Typical assays used to discover and analyze small molecules that inhibit the hepatitis C virus (HCV) NS3 helicase yield few hits and are often confounded by compound interference. Oligonucleotide binding assays are examined here as an alternative. After comparing fluorescence polarization (FP), homogeneous time-resolved fluorescence (HTRF®; Cisbio) and AlphaScreen® (Perkin Elmer) assays, an FP-based assay was chosen to screen Sigma's Library of Pharmacologically Active Compounds (LOPAC) for compounds that inhibit NS3-DNA complex formation. Four LOPAC compounds inhibited the FP-based assay: aurintricarboxylic acid (ATA) (IC50=1.4 μM), suramin sodium salt (IC50=3.6 μM), NF 023 hydrate (IC50=6.2 μM) and tyrphostin AG 538 (IC50=3.6 μM). All but AG 538 inhibited helicase-catalyzed strand separation, and all but NF 023 inhibited replication of subgenomic HCV replicons. A counterscreen using Escherichia coli single-stranded DNA binding protein (SSB) revealed that none of the new HCV helicase inhibitors were specific for NS3h. However, when the SSB-based assay was used to analyze derivatives of another non-specific helicase inhibitor, the main component of the dye primuline, it revealed that some primuline derivatives (e.g. PubChem CID50930730) are up to 30-fold more specific for HCV NS3h than similarly potent HCV helicase inhibitors.

Indexed as

High-Throughput Screening AssaysDEAD-box RNA HelicasesDNADNA-Binding ProteinsEnzyme AssaysEnzyme InhibitorsEscherichia coli ProteinsFluorescence PolarizationHepacivirusNucleoside-TriphosphataseRNA HelicasesSerine EndopeptidasesSmall Molecule LibrariesViral Nonstructural ProteinsViral ProteasesDEAD-box RNA HelicasesDNADNA-Binding ProteinsEnzyme InhibitorsEscherichia coli ProteinsNS3 protein, hepatitis C virusNucleoside-TriphosphataseRNA HelicasesSerine EndopeptidasesSmall Molecule LibrariesSSB protein, E coliViral Nonstructural ProteinsViral Proteases

Identifiers

PMID22740655
PMCPMC3458564
OpenAlexW2144736968

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.