ArticleAntimicrobial agents and chemotherapy2016
Barrier-Independent, Fitness-Associated Differences in Sofosbuvir Efficacy against Hepatitis C Virus.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 50 citations in OpenAlex.
- Peaked-to-flat transition in quasispecies structure evolution.Virus evolution · 2026Article
- Viral Quasispecies Inference from Single Observations-Mutagens as Accelerators of Quasispecies Evolution.Microorganisms · 2025Article
- SARS-CoV-2 Remdesivir Exposure Leads to Different Evolutionary Pathways That Converge in Moderate Levels of Drug Resistance.Viruses · 2025Article
- Characteristics of a Chinese Cohort of Patients with Chronic Hepatitis C Infection (2019-2023) and a Case Report of Resistance-associated Substitutions to Sofosbuvir-velpatasvir Treatment.Journal of clinical and translational hepatology · 2025Article
- Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies.Microorganisms · 2024Article
- Fitness-Dependent, Mild Mutagenic Activity of Sofosbuvir for Hepatitis C Virus.Antimicrobial agents and chemotherapy · 2023Article
- Hepatitis C virus fitness can influence the extent of infection-mediated epigenetic modifications in the host cells.Frontiers in cellular and infection microbiology · 2023Article
- Quasispecies Fitness Partition to Characterize the Molecular Status of a Viral Population. Negative Effect of Early Ribavirin Discontinuation in a Chronically Infected HEV Patient.International journal of molecular sciences · 2022Article
- The apparent interferon resistance of transmitted HIV-1 is possibly a consequence of enhanced replicative fitness.PLoS pathogens · 2022Article
- SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations.Pathogens (Basel, Switzerland) · 2022Article
- Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture.Frontiers in microbiology · 2022Article
- Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools.PLoS pathogens · 2022Article
- A Two-Level, Intramutant Spectrum Haplotype Profile of Hepatitis C Virus Revealed by Self-Organized Maps.Microbiology spectrum · 2021Article
- Review
- Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro.International journal of molecular sciences · 2021Article
- Amino Acid Substitutions Associated with Treatment Failure for Hepatitis C Virus Infection.Journal of clinical microbiology · 2020Article
- Broad and Dynamic Diversification of Infectious Hepatitis C Virus in a Cell Culture Environment.Journal of virology · 2020Article
- Prevalence of Naturally-Occurring NS5A and NS5B Resistance-Associated Substitutions in Iranian Patients With Chronic Hepatitis C Infection.Frontiers in microbiology · 2020Article
- Synergistic lethal mutagenesis of hepatitis C virus.Antimicrobial agents and chemotherapy · 2019Article
- Toll-Like Receptor 7 (TLR-7) and TLR-9 Agonists Improve Hepatitis C Virus Replication and Infectivity Inhibition by Plasmacytoid Dendritic Cells.Journal of virology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Sofosbuvir displays a high phenotypic barrier to resistance, and it is a component of several combination therapies for hepatitis C virus (HCV) infections. HCV fitness can be a determinant of decreased sensitivity to direct-acting antiviral agents such as telaprevir or daclatasvir, but fitness-dependent decreased drug sensitivity has not been established for drugs with a high phenotypic barrier to resistance. Low- and high-fitness HCV populations and biological clones derived from them were used to infect Huh-7.5 hepatoma cells. Sofosbuvir efficacy was analyzed by measuring virus progeny production during several passages and by selection of possible sofosbuvir resistance mutations determined by sequencing the NS5B-coding region of the resulting populations. Sofosbuvir exhibited reduced efficacy against high-fitness HCV populations, without the acquisition of sofosbuvir-specific resistance mutations. A reduced sofosbuvir efficacy, similar to that observed with the parental populations, was seen for high-fitness individual biological clones. In independently derived high-fitness HCV populations or clones passaged in the presence of sofosbuvir, M289L was selected as the only substitution in the viral polymerase NS5B. In no case was the sofosbuvir-specific resistance substitution S282T observed. High HCV fitness can lead to decreased sensitivity to sofosbuvir, without the acquisition of specific sofosbuvir resistance mutations. Thus, fitness-dependent drug sensitivity can operate with HCV inhibitors that display a high barrier to resistance. This mechanism may underlie treatment failures not associated with selection of sofosbuvir-specific resistance mutations, linked to in vivo fitness of pretreatment viral populations.
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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.