ArticleAntimicrobial agents and chemotherapy2012
Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03283176 (Changes in Hematologic Profile, Vitamin B12 and Folic Acid Level in Cirrhotic Patients Received Sofosbuvir and Daclatasvir With or Without Ribavirin), which is not on this map. Cited by 106 papers.
What it found
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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.
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.
Changes in Hematologic Profile, Vitamin B12 and Folic Acid Level in Cirrhotic Patients Received Sofosbuvir and Daclatasvir With or Without Ribavirin
Who cites it
106 citing papers in PubMed, 241 citations in OpenAlex.
- Efficacy and safety of sofosbuvir/ ledipasvir in treatment of patients with COVID-19; A randomized clinical trial.Acta bio-medica : Atenei Parmensis · 2020Trial
- Efficacy and safety of ledipasvir/sofosbuvir with ribavirin in chronic hepatitis C patients who failed daclatasvir/asunaprevir therapy: pilot study.Journal of gastroenterology · 2018Trial
- Infrequent development of resistance in genotype 1-6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014Trial
- Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study.Annals of internal medicine · 2014Trial
- Towards broader-spectrum direct-acting antivirals against RNA viruses.Nature reviews. Microbiology · 2026Review
- Identification of NS5B resistance-associated mutations in hepatitis C virus circulating in treatment-naïve Cameroonian patients.IJID regions · 2026Article
- Prodrug strategies in developing antiviral nucleoside analogs.RSC medicinal chemistry · 2026Review
- Mechanism of Inhibition of the Active Triphosphate Form of 2'-α-Fluoro,2'-β-bromouridine against Yellow Fever Virus RNA-Dependent RNA Polymerase.ACS infectious diseases · 2025Article
- Article
- West Nile virus - a re-emerging global threat: recent advances in vaccines and drug discovery.Frontiers in cellular and infection microbiology · 2025Review
- Review
- Fitness-Dependent, Mild Mutagenic Activity of Sofosbuvir for Hepatitis C Virus.Antimicrobial agents and chemotherapy · 2023Article
- Review
- Direct antiviral agents (DAAs) and their use in pregnant women with hepatitis C (HCV).Expert review of anti-infective therapy · 2022Review
- RNA-Dependent RNA Polymerase of the Second Human Pegivirus Exhibits a High-Fidelity Feature.Microbiology spectrum · 2022Article
- The Inhibitory Potential of 2'-dihalo Ribonucleotides against HCV: Molecular Docking, Molecular Simulations, MM-BPSA, and DFT Studies.Molecules (Basel, Switzerland) · 2022Article
- Phylogenetic signature and prevalence of natural resistance-associated substitutions for hepatitis C virus genotypes 3a and 3b in southwestern China.Journal of virus eradication · 2022Article
- Molecular dynamics simulations and MM-GBSA reveal novel guanosine derivatives against SARS-CoV-2 RNA dependent RNA polymerase.RSC advances · 2022Article
- The Role of RASs /RVs in the Current Management of HCV.Viruses · 2021Review
- An evaluation of ledipasvir + sofosbuvir for the treatment of chronic hepatitis C infection.Expert opinion on pharmacotherapy · 2021Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PSI-7977, a prodrug of 2'-F-2'-C-methyluridine monophosphate, is the purified diastereoisomer of PSI-7851 and is currently being investigated in phase 3 clinical trials for the treatment of hepatitis C. In this study, we profiled the activity of PSI-7977 and its ability to select for resistance using a number of different replicon cells. Results showed that PSI-7977 was active against genotype (GT) 1a, 1b, and 2a (strain JFH-1) replicons and chimeric replicons containing GT 2a (strain J6), 2b, and 3a NS5B polymerase. Cross-resistance studies using GT 1b replicons confirmed that the S282T change conferred resistance to PSI-7977. Subsequently, we evaluated the ability of PSI-7977 to select for resistance using GT 1a, 1b, and 2a (JFH-1) replicon cells. S282T was the common mutation selected among all three genotypes, but while it conferred resistance to PSI-7977 in GT 1a and 1b, JFH-1 GT 2a S282T showed only a very modest shift in 50% effective concentration (EC(50)) for PSI-7977. Sequence analysis of the JFH-1 NS5B region indicated that additional amino acid changes were selected both prior to and after the emergence of S282T. These include T179A, M289L, I293L, M434T, and H479P. Residues 179, 289, and 293 are located within the finger and palm domains, while 434 and 479 are located on the surface of the thumb domain. Data from the JFH-1 replicon variants showed that amino acid changes within the finger and palm domains together with S282T were required to confer resistance to PSI-7977, while the mutations on the thumb domain serve to enhance the replication capacity of the S282T replicons.
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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.