ArticlePloS one2015
Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV antiviral agent.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- KASL clinical practice guidelines: management of hepatitis C.Clinical and molecular hepatology · 2016Guideline
- Successful Retreatment of Chronic HCV Genotype-1 Infection With Ledipasvir and Sofosbuvir After Initial Short Course Therapy With Direct-Acting Antiviral Regimens.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Trial
- A novel dimerization site in non-structural protein 5A of hepatitis C virus regulates viral replication fitness.PLoS pathogens · 2026Article
- Pharmacogenomics of antibacterial and antiviral therapies: Clinical actionability, evidence gaps, and future directions.Pharmacological reviews · 2026Review
- Phospholipid-driven conformational switching of HCV NS5A links protein folding to replication membrane remodeling.Science advances · 2026Article
- Identification of novel compounds againstComputational and structural biotechnology journal · 2025Article
- Ledipasvir/Sofosbuvir Is Effective for Relapsed Genotype 1b Hepatitis C Virus Patients after Achieving a Sustained Virological Response at Post-treatment Week 12 with Glecaprevir/Pibrentasvir.Internal medicine (Tokyo, Japan) · 2023Article
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- Validated Reversed-Phase Liquid Chromatographic Method with Gradient Elution for Simultaneous Determination of the Antiviral Agents: Sofosbuvir, Ledipasvir, Daclatasvir, and Simeprevir in Their Dosage Forms.Molecules (Basel, Switzerland) · 2020Article
- Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets.Viruses · 2019Review
- Hepatitis C resistance to NS5A inhibitors: Is it going to be a problem?World journal of hepatology · 2018Article
- Grazoprevir/elbasvir treatment for the relapse of HCV genotype 1b infection after ledipasvir/sofosbuvir: A case report.Experimental and therapeutic medicine · 2018Article
- Characterization of the Anti-Hepatitis C Virus Activity of New Nonpeptidic Small-Molecule Cyclophilin Inhibitors with the Potential for Broad Anti-Flaviviridae Activity.Antimicrobial agents and chemotherapy · 2018Article
- The hepatitis C viral nonstructural protein 5A stabilizes growth-regulatory human transcripts.Nucleic acids research · 2018Article
- Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years.Molecules (Basel, Switzerland) · 2017Review
- Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use.Drugs · 2017Review
- An insight into the molecular characteristics of hepatitis C virus for clinicians.Saudi medical journal · 2016Review
- In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir.Antimicrobial agents and chemotherapy · 2016Article
- Synergistic Activity of Combined NS5A Inhibitors.Antimicrobial agents and chemotherapy · 2015Article
- Virologic Tools for HCV Drug Resistance Testing.Viruses · 2015Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ledipasvir, a direct acting antiviral agent (DAA) targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H) that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants.
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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.