Related Experiment Video
Updated: May 15, 2026
11:34
High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C
Edward J Gane1, Catherine A Stedman, Robert H Hyland
1New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand. edgane@adhb.govt.nz
The New England Journal of Medicine
|January 4, 2013
Summary
Sofosbuvir combined with ribavirin offers a highly effective treatment for hepatitis C virus (HCV) infection, achieving a 100% sustained virologic response in previously untreated patients across genotypes 1, 2, and 3.
Area of Science:
- Hepatology
- Virology
- Pharmacology
Background:
- Standard hepatitis C virus (HCV) treatment involves interferon, which has limitations due to administration route and side effects.
- Sofosbuvir, an oral nucleotide inhibitor, presents an alternative therapeutic option for HCV infection.
- Evaluation of sofosbuvir in interferon-sparing and interferon-free regimens is crucial for improving patient outcomes.
Purpose of the Study:
- To assess the efficacy of sofosbuvir in combination with ribavirin and/or peginterferon alfa-2a for treating HCV infection.
- To determine sustained virologic response rates in patients with HCV genotypes 1, 2, and 3 receiving different sofosbuvir-based regimens.
- To compare the effectiveness of sofosbuvir-based treatments with and without interferon.
Main Methods:
- Open-label study involving eight groups of patients with HCV genotypes 1, 2, or 3.
- Randomized assignment of 40 previously untreated patients (genotypes 2 or 3) to sofosbuvir plus ribavirin for 12 weeks, with or without peginterferon alfa-2a for varying durations.
- Treatment arms included sofosbuvir monotherapy, sofosbuvir plus peginterferon alfa-2a and ribavirin, and sofosbuvir plus ribavirin in treatment-experienced and treatment-naive patients with genotype 1 HCV.
Main Results:
- A 100% sustained virologic response (SVR) at 24 weeks was observed in patients receiving sofosbuvir plus ribavirin without interferon (genotype 2 or 3).
- High SVR rates (100%) were also achieved with sofosbuvir plus ribavirin and interferon (4-12 weeks) and sofosbuvir plus peginterferon alfa-2a and ribavirin (8 weeks) in genotype 2 or 3 patients.
- In genotype 1 patients, SVR rates were 84% for previously untreated individuals and 10% for those with prior treatment failure when treated with sofosbuvir and ribavirin for 12 weeks.
Conclusions:
- Sofosbuvir plus ribavirin for 12 weeks demonstrates potential efficacy in previously untreated patients with HCV genotypes 1, 2, or 3.
- These findings suggest that sofosbuvir-based regimens can be effective alternatives to interferon-based therapies.
- Further research may explore optimized sofosbuvir regimens for different HCV genotypes and patient populations.
Related Concept Videos
01:30Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
01:25Hepatitis
Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
01:28Viral Hepatitis I: Introduction
Viral hepatitis is an inflammatory condition of the liver caused by infection with hepatotropic viruses, most commonly hepatitis A, B, C, D, and E. Despite variations in structure and transmission, all viruses mentioned infect hepatocytes and provoke immune responses that can hinder liver function. Additionally, some non-hepatotropic viruses can also lead to hepatic inflammation.Hepatitis A VirusHepatitis A virus (HAV) is transmitted through the fecal–oral route, typically by ingestion of food...
01:29Subviral Agents
Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
01:28Inhibitors of Bacterial DNA Synthesis
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
01:29Viruses with RNA Genomes
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...