ArticleAntimicrobial agents and chemotherapy2008
Development of intergenotypic chimeric replicons to determine the broad-spectrum antiviral activities of hepatitis C virus polymerase inhibitors.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 48 citations in OpenAlex.
- Pharmacokinetics, pharmacodynamics, and tolerability of GS-9851, a nucleotide analog polymerase inhibitor, following multiple ascending doses in patients with chronic hepatitis C infection.Antimicrobial agents and chemotherapy · 2013Trial
- Preclinical characterization of GS-9669, a thumb site II inhibitor of the hepatitis C virus NS5B polymerase.Antimicrobial agents and chemotherapy · 2013Trial
- RNA-Dependent RNA Polymerase of the Second Human Pegivirus Exhibits a High-Fidelity Feature.Microbiology spectrum · 2022Article
- HCV Replicon Systems: Workhorses of Drug Discovery and Resistance.Frontiers in cellular and infection microbiology · 2020Review
- Review
- Potency and resistance analysis of hepatitis C virus NS5B polymerase inhibitor BMS-791325 on all major genotypes.Antimicrobial agents and chemotherapy · 2014Article
- Cross-genotypic examination of hepatitis C virus polymerase inhibitors reveals a novel mechanism of action for thumb binders.Antimicrobial agents and chemotherapy · 2014Article
- Preclinical characterization of BMS-791325, an allosteric inhibitor of hepatitis C Virus NS5B polymerase.Antimicrobial agents and chemotherapy · 2014Article
- Robust and persistent replication of the genotype 6a hepatitis C virus replicon in cell culture.Antimicrobial agents and chemotherapy · 2014Article
- Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.Antimicrobial agents and chemotherapy · 2014Article
- Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus.Antimicrobial agents and chemotherapy · 2012Article
- Origin and evolution of the unique hepatitis C virus circulating recombinant form 2k/1b.Journal of virology · 2012Article
- Cell penetrable humanized-VH/V(H)H that inhibit RNA dependent RNA polymerase (NS5B) of HCV.PloS one · 2012Article
- Inhibition of hepatitis C virus replication by Monascus pigment derivatives that interfere with viral RNA polymerase activity and the mevalonate biosynthesis pathway.The Journal of antimicrobial chemotherapy · 2012Article
- Activity and the metabolic activation pathway of the potent and selective hepatitis C virus pronucleotide inhibitor PSI-353661.Antiviral research · 2011Article
- PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication.Antimicrobial agents and chemotherapy · 2010Article
- 1a/1b subtype profiling of nonnucleoside polymerase inhibitors of hepatitis C virus.Journal of virology · 2010Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To address the need for broad-spectrum antiviral activity characterization of hepatitis C virus (HCV) polymerase inhibitors, we created a panel of intergenotypic chimeric replicons containing nonstructural (NS) protein NS5B sequences from genotype 2b (GT2b), GT3a, GT4a, GT5a, and GT6a HCV isolates. Viral RNA extracted from non-GT1 HCV patient plasma was subjected to reverse transcription. The NS5B region was amplified by nested PCR and introduced into the corresponding region of the GT1b (Con-1) subgenomic reporter replicon by Splicing by Overlap Extension (SOEing) PCR. Stable cell lines were generated with replication-competent chimeras for in vitro antiviral activity determination of HCV nonnucleoside polymerase inhibitors (NNIs) that target different regions of the protein. Compounds that bind to the NNI2 (thiophene carboxylic acid) or NNI3 (benzothiadiazine) allosteric sites showed 8- to >1,280-fold reductions in antiviral activity against non-GT1 NS5B chimeric replicons compared to that against the GT1b subgenomic replicon. Smaller reductions in susceptibility, ranging from 0.2- to 33-fold, were observed for the inhibitor binding to the NNI1 (benzimidazole) site. The inhibitor binding to the NNI4 (benzofuran) site showed broad-spectrum antiviral activity against all chimeric replicons evaluated in this study. In conclusion, evaluation of HCV NNIs against intergenotypic chimeric replicons showed differences in activity spectrum for inhibitors that target different regions of the enzyme, some of which could be associated with specific residues that differ between GT1 and non-GT1 polymerases. Our study demonstrates the utility of chimeric replicons for broad-spectrum activity determination of HCV inhibitors.
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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.