ArticleJournal of virology2011
Small molecules targeting hepatitis C virus-encoded NS5A cause subcellular redistribution of their target: insights into compound modes of action.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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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.
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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
57 citing papers in PubMed.
- Intracellular "In Silico Microscopes"-Comprehensive 3D Spatio-Temporal Virus Replication Model Simulations.Viruses · 2024Article
- Efficient Estimates of Surface Diffusion Parameters for Spatio-Temporally Resolved Virus Replication Dynamics.International journal of molecular sciences · 2024Article
- Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus.Viruses · 2023Article
- Regulatory Role of Phospholipids in Hepatitis C Virus Replication and Protein Function.Pathogens (Basel, Switzerland) · 2022Review
- Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Article
- Effect of P-body component Mov10 on HCV virus production and infectivity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Critical Assessment of Targeted Protein Degradation as a Research Tool and Pharmacological Modality.Trends in pharmacological sciences · 2020Review
- Advanced Hepatitis C Virus Replication PDE Models within a Realistic Intracellular Geometric Environment.International journal of environmental research and public health · 2019Article
- Era of direct acting anti-viral agents for the treatment of hepatitis C.World journal of hepatology · 2018Review
- NS5A Promotes Constitutive Degradation of IP3R3 to Counteract Apoptosis Induced by Hepatitis C Virus.Cell reports · 2018Article
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- Modulation of Cell Death Pathways by Hepatitis C Virus Proteins in Huh7.5 Hepatoma Cells.International journal of molecular sciences · 2017Article
- 3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle.Viruses · 2017Article
- Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use.Drugs · 2017Review
- NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains.PLoS pathogens · 2017Article
- Applications of chemogenomic library screening in drug discovery.Nature reviews. Drug discovery · 2017Review
- Continuous de novo generation of spatially segregated hepatitis C virus replication organelles revealed by pulse-chase imaging.Journal of hepatology · 2017Article
- Human Choline Kinase-α Promotes Hepatitis C Virus RNA Replication through Modulation of Membranous Viral Replication Complex Formation.Journal of virology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The current standard of care for hepatitis C virus (HCV)-infected patients consists of lengthy treatment with interferon and ribavirin. To increase the effectiveness of HCV therapy, future regimens will incorporate multiple direct-acting antiviral (DAA) drugs. Recently, the HCV-encoded NS5A protein has emerged as a promising DAA target. Compounds targeting NS5A exhibit remarkable potency in vitro and demonstrate early clinical promise, suggesting that NS5A inhibitors could feature in future DAA combination therapies. Since the mechanisms through which these molecules operate are unknown, we have used NS5A inhibitors as tools to investigate their modes of action. Analysis of replicon-containing cells revealed dramatic phenotypic alterations in NS5A localization following treatment with NS5A inhibitors; NS5A was redistributed from the endoplasmic reticulum to lipid droplets. The NS5A relocalization did not occur in cells treated with other classes of HCV inhibitors, and NS5A-targeting molecules did not cause similar alterations in the localization of other HCV-encoded proteins. Time course analysis of the redistribution of NS5A revealed that the transfer of protein to lipid droplets was concomitant with the onset of inhibition, as judged by the kinetic profiles for these compounds. Furthermore, analysis of the kinetic profile of inhibition for a panel of test molecules permitted the separation of compounds into different kinetic classes based on their modes of action. Results from this approach suggested that NS5A inhibitors perturbed the function of new replication complexes, rather than acting on preformed complexes. Taken together, our data reveal novel biological consequences of NS5A inhibition, which may help enable the development of future assay platforms for the identification of new and/or different NS5A 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.