Evidence map›Paper›PMID 20108979›Full record

ArticleBiochemistry2010

Mechanism and specificity of a symmetrical benzimidazolephenylcarboxamide helicase inhibitor.

Craig A Belon, Yoji D High, Tse-I Lin, Frederik Pauwels, David N Frick

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.5field-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

22 citing papers in PubMed, 31 citations in OpenAlex.

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  20. Antiviral drugs against hepatitis C virus.Genetic vaccines and therapy · 2011
    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

5 authors at 1 institution in 1 country.

Craig A BelonDepartment of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA.
Yoji D High
Tse-I Lin
Frederik Pauwels
David N Frick
New York Medical College · US

Funding

Enzymatic Differences Among Hepatitis C Virus GenotypesR01AI052395 · NIAID · NEW YORK MEDICAL COLLEGE · PI FRICK, DAVID N · 2003 to 2007
$1.5M
Hepatitis C VIrus NS3 Helicase Inhibitor DiscoveryR03MH085690 · NIMH · NEW YORK MEDICAL COLLEGE · PI FRICK, DAVID N · 2008 to 2008
$25k
NIAID NIH HHS AI052395NIAID NIH HHS R01 AI052395NIMH NIH HHS MH085690NIMH NIH HHS R03 MH085690
6 · The paper itself

Abstract

This study examines the effects of 1-N,4-N-bis[4-(1H-benzimidazol-2-yl)phenyl]benzene-1,4-dicarboxamide ((BIP)(2)B) on the NS3 helicase encoded by the hepatitis C virus (HCV). Molecular beacon-based helicase assays were used to show that (BIP)(2)B inhibits the ability of HCV helicase to separate a variety of RNA and DNA duplexes with half-maximal inhibitory concentrations ranging from 0.7 to 5 microM, depending on the nature of the substrate. In single turnover assays, (BIP)(2)B only inhibited unwinding reactions when it was preincubated with the helicase-nucleic acid complex. (BIP)(2)B quenched NS3 intrinsic protein fluorescence with an apparent dissociation constant of 5 microM, and in the presence of (BIP)(2)B, HCV helicase did not appear to interact with a fluorescent DNA oligonucleotide. In assays monitoring HCV helicase-catalyzed ATP hydrolysis, (BIP)(2)B only inhibited helicase-catalyzed ATP hydrolysis in the presence of intermediate concentrations of RNA, suggesting RNA and (BIP)(2)B compete for the same binding site. HCV helicases isolated from various HCV genotypes were similarly sensitive to (BIP)(2)B, with half-maximal inhibitory concentrations ranging from 0.7 to 2.4 microM. (BIP)(2)B also inhibited ATP hydrolysis catalyzed by related helicases from Dengue virus, Japanese encephalitis virus, and humans. (BIP)(2)B appeared to bind the HCV and human proteins with similar affinity (K(i) = 7 and 8 microM, respectively), but it bound the flavivirus proteins up to 270 times more tightly. Results are discussed in light of a molecular model of a (BIP)(2)B-HCV helicase complex, which is unable to bind nucleic acid, thus preventing the enzyme from separating double-stranded nucleic acid.

Indexed as

Antiviral AgentsBase SequenceBenzimidazolesCatalysisDEAD-box RNA HelicasesHepacivirusHumansModels, MolecularMolecular Sequence DataNucleoside-TriphosphataseRNA HelicasesSerine EndopeptidasesSubstrate SpecificityViral Nonstructural ProteinsViral Proteases1-N,4-N-bis(4-(1H-benzimidazol-2-yl)phenyl)benzene-1,4-dicarboxamideAntiviral AgentsBenzimidazolesDEAD-box RNA HelicasesNS3 protein, hepatitis C virusNucleoside-TriphosphataseRNA HelicasesSerine EndopeptidasesViral Nonstructural ProteinsViral Proteases

Identifiers

PMID20108979
PMCPMC2832472
OpenAlexW2049082208

What OpenQuestion holds

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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.