Trial reportJournal of virology2013
Deep sequencing reveals mutagenic effects of ribavirin during monotherapy of hepatitis C virus genotype 1-infected patients.
Trial report in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 95 citations in OpenAlex.
- Mutations Identified in the Hepatitis C Virus (HCV) Polymerase of Patients with Chronic HCV Treated with Ribavirin Cause Resistance and Affect Viral Replication Fidelity.Antimicrobial agents and chemotherapy · 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
- Hepatic Pharmacokinetics and Pharmacodynamics With Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir Treatment and Variable Ribavirin Dosage.The Journal of infectious diseases · 2018Trial
- Evolution of hepatitis C virus quasispecies during repeated treatment with the NS3/4A protease inhibitor telaprevir.Antimicrobial agents and chemotherapy · 2015Trial
- Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection.Hepatology (Baltimore, Md.) · 2014Trial
- Crimean-Congo haemorrhagic fever (CCHF): present and future therapeutic armamentarium.Le infezioni in medicina · 2024Review
- Atypical Mutational Spectrum of SARS-CoV-2 Replicating in the Presence of Ribavirin.Antimicrobial agents and chemotherapy · 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
- Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity.Viruses · 2022Review
- Favipiravir Inhibits Hepatitis A Virus Infection in Human Hepatocytes.International journal of molecular sciences · 2022Article
- Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools.PLoS pathogens · 2022Article
- Controversies' clarification regarding ribavirin efficacy in measles and coronaviruses: Comprehensive therapeutic approach strictly tailored to COVID-19 disease stages.World journal of clinical cases · 2021Article
- Review
- Potential molecular targets of nonstructural proteins for the development of antiviral drugs against SARS-CoV-2 infection.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Synergistic lethal mutagenesis of hepatitis C virus.Antimicrobial agents and chemotherapy · 2019Article
- Article
- Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs.Antimicrobial agents and chemotherapy · 2018Article
- Quasispecies characters of hepatitis B virus in immunoprophylaxis failure infants.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2018Article
- Nucleobases and corresponding nucleosides display potent antiviral activities against dengue virus possibly through viral lethal mutagenesis.PLoS neglected tropical diseases · 2018Article
- Antiviral Effect of Ribavirin against HCV Associated with Increased Frequency of G-to-A and C-to-U Transitions in Infectious Cell Culture Model.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The preeminent mode of action of the broad-spectrum antiviral nucleoside ribavirin in the therapy of chronic hepatitis C is currently unresolved. Particularly under contest are possible mutagenic effects of ribavirin that may lead to viral extinction by lethal mutagenesis of the hepatitis C virus (HCV) genome. We applied ultradeep sequencing to determine ribavirin-induced sequence changes in the HCV coding region (nucleotides [nt] 330 to 9351) of patients treated with 6-week ribavirin monotherapy (n = 6) in comparison to placebo (n = 6). Baseline HCV RNA levels maximally declined on average by -0.8 or -0.1 log10 IU/ml in ribavirin- versus placebo-treated patients. No general increase in rates of nucleotide substitutions in ribavirin-treated patients was observed. However, more HCV genome positions with high G-to-A and C-to-U transition rates were detected between baseline and treatment week 6 in ribavirin-treated patients in comparison to placebo-treated patients (rate of 0.0041 transitions per base pair versus rate of 0.0022 transitions per base pair; P = 0.049). Similarly, the sensitive detection of low-frequency minority variants by statistical filtering indicated significantly more positions with G-to-A and C-to-U transitions in ribavirin-treated patients than in placebo-treated patients (rate of 0.0331 transitions versus rate of 0.0186 transitions per G/C-containing position at baseline; P = 0.018). In contrast, non-ribavirin-associated A-to-G and U-to-C transitions were not enriched in the ribavirin group (P = 0.152). We conclude that ribavirin exerts a mutagenic effect on the virus in patients with chronic hepatitis C by facilitating G-to-A and C-to-U nucleotide transitions.
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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.