ArticleAntimicrobial agents and chemotherapy2015
Fast hepatitis C virus RNA elimination and NS5A redistribution by NS5A inhibitors studied by a multiplex assay approach.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 19 citations in OpenAlex.
- The paradox of highly effective sofosbuvir-based combination therapy despite slow viral decline: can we still rely on viral kinetics?Scientific reports · 2017Trial
- Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus.Viruses · 2023Article
- TMEM41B Is a Pan-flavivirus Host Factor.Cell · 2021Article
- TMEM41B is a pan-flavivirus host factor.bioRxiv : the preprint server for biology · 2020Article
- Crippling life support for SARS-CoV-2 and other viruses through synthetic lethality.The Journal of cell biology · 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
- Effect of Low Positive End of Treatment Viral Load with Direct-Acting Antiviral Therapy on Sustained Virologic Response.Canadian journal of gastroenterology & hepatology · 2020Article
- Article
- NS5A Promotes Constitutive Degradation of IP3R3 to Counteract Apoptosis Induced by Hepatitis C Virus.Cell reports · 2018Article
- Modeling how reversal of immune exhaustion elicits cure of chronic hepatitis C after the end of treatment with direct-acting antiviral agents.Immunology and cell biology · 2018Article
- Interferon at the cellular, individual, and population level in hepatitis C virus infection: Its role in the interferon-free treatment era.Immunological reviews · 2018Review
- Article
- NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains.PLoS pathogens · 2017Article
- Approved Antiviral Drugs over the Past 50 Years.Clinical microbiology reviews · 2016Review
- Inhibitory activity of limonoids fromAvicenna journal of phytomedicineArticle
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
While earlier therapeutic strategies for the treatment of hepatitis C virus (HCV) infection relied exclusively on interferon (IFN) and ribavirin (RBV), four direct-acting antiviral agents (DAAs) have now been approved, aiming for an interferon-free strategy with a short treatment duration and fewer side effects. To facilitate studies on the mechanism of action (MOA) and efficacy of DAAs, we established a multiplex assay approach, which employs flow cytometry, a Gaussia luciferase reporter system, Western blot analysis, reverse transcription-quantitative PCR (RT-qPCR), a limited dilution assay (50% tissue culture infectious dose [TCID50]), and an image profiling assay that follows the NS5A redistribution in response to drug treatment. We used this approach to compare the relative potency of various DAAs and the kinetics of their antiviral effects as a potential preclinical measure of their potential clinical utility. We evaluated the NS5A inhibitors ledipasvir (LDV) and daclatasvir (DCV), the NS3/4A inhibitor danoprevir (DNV), and the NS5B inhibitor sofosbuvir (SOF). In terms of kinetics, our data demonstrate that the NS5A inhibitor LDV, followed closely by DCV, has the fastest effect on suppression of viral proteins and RNA and on redistribution of NS5A. In terms of MOA, LDV has a more pronounced effect than DCV on the viral replication, assembly, and infectivity of released virus. Our approach can be used to facilitate the study of the biological processes involved in HCV replication and help identify optimal drug combinations.
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Registered trials
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.