ArticlePLoS computational biology2013
Analysis of hepatitis C virus decline during treatment with the protease inhibitor danoprevir using a multiscale model.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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.
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.
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Who cites it
56 citing papers in PubMed, 92 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
- Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens.PloS one · 2017Trial
- Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study.The lancet. Gastroenterology & hepatology · 2016Trial
- Modelling the interaction between danoprevir and mericitabine in the treatment of chronic HCV infection.Antiviral therapy · 2016Trial
- A pharmacokinetic/viral kinetic model to evaluate the treatment effectiveness of danoprevir against chronic HCV.Antiviral therapy · 2015Trial
- Multiscale Modeling of an 8-Week Combination Regimen of Bemnifosbuvir and Ruzasvir in Patients with Chronic Hepatitis C Virus Infection.Clinical pharmacology and therapeutics · 2026Article
- Bemnifosbuvir: An HCV NS5B Inhibitor With Multiple Modes of Action.Clinical pharmacology and therapeutics · 2026Article
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- INHERITANCE OF INTRACELLULAR VIRAL RNA IN A MULTISCALE MODEL OF HEPATITIS C INFECTION.SIAM journal on applied mathematics · 2026Article
- A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B.PLoS computational biology · 2025Article
- Intracellular "In Silico Microscopes"-Comprehensive 3D Spatio-Temporal Virus Replication Model Simulations.Viruses · 2024Article
- The reproduction number and its probability distribution for stochastic viral dynamics.Journal of the Royal Society, Interface · 2024Article
- Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities.Molecular pharmaceutics · 2023Review
- Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors.International journal of molecular sciences · 2023Article
- Computational modeling of protracted HCMV replication using genome substrates and protein temporal profiles.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Advances in Parameter Estimation and Learning from Data for Mathematical Models of Hepatitis C Viral Kinetics.Mathematics (Basel, Switzerland) · 2022Article
- Machine learning for mathematical models of HCV kinetics during antiviral therapy.Mathematical biosciences · 2022Article
- Intra- and Inter-cellular Modeling of Dynamic Interaction between Zika Virus and Its Naturally Occurring Defective Viral Genomes.Journal of virology · 2021Article
- Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection.Scientific reports · 2021Article
- Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
Abstract
The current paradigm for studying hepatitis C virus (HCV) dynamics in patients utilizes a standard viral dynamic model that keeps track of uninfected (target) cells, infected cells, and virus. The model does not account for the dynamics of intracellular viral replication, which is the major target of direct-acting antiviral agents (DAAs). Here we describe and study a recently developed multiscale age-structured model that explicitly considers the potential effects of DAAs on intracellular viral RNA production, degradation, and secretion as virus into the circulation. We show that when therapy significantly blocks both intracellular viral RNA production and virus secretion, the serum viral load decline has three phases, with slopes reflecting the rate of serum viral clearance, the rate of loss of intracellular viral RNA, and the rate of loss of intracellular replication templates and infected cells, respectively. We also derive analytical approximations of the multiscale model and use one of them to analyze data from patients treated for 14 days with the HCV protease inhibitor danoprevir. Analysis suggests that danoprevir significantly blocks intracellular viral production (with mean effectiveness 99.2%), enhances intracellular viral RNA degradation about 5-fold, and moderately inhibits viral secretion (with mean effectiveness 56%). The multiscale model can be used to study viral dynamics in patients treated with other DAAs and explore their mechanisms of action in treatment of hepatitis C.
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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.