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Subviral Agents

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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...

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Updated: Dec 25, 2025

A Protocol for Analyzing Hepatitis C Virus Replication

A Protocol for Analyzing Hepatitis C Virus Replication

Published on: June 26, 2014

GSK2818713, a Novel Biphenylene Scaffold-Based Hepatitis C NS5A Replication Complex Inhibitor with Broad Genotype

Wieslaw M Kazmierski¹, Sam Baskaran¹, Jill T Walker¹

¹GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, North Carolina 27709, United States.

Journal of Medicinal Chemistry

|March 24, 2020

Summary

GSK2818713 is a novel hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor with broad genotype coverage. It demonstrates potent and durable reduction of HCV RNA, advancing as a preclinical candidate.

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A Protocol for Analyzing Hepatitis C Virus Replication

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Published on: June 26, 2014

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Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds

Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds

Published on: October 29, 2015

Area of Science:

Virology
Medicinal Chemistry
Drug Discovery

Background:

Hepatitis C virus (HCV) treatment relies on pan-genotype nonstructural protein 5A (NS5A) inhibitors.
First-generation NS5A inhibitors like daclatasvir (DCV) have limitations in genotype coverage.

Purpose of the Study:

To detail the discovery and characterization of GSK2818713 (13), a novel NS5A inhibitor.
To evaluate GSK2818713's improved genotype coverage and preclinical potential.

Main Methods:

Structure-activity relationship (SAR) analysis was performed.
Activity against various HCV genotypes and chimeric replicons was assessed.
Long-term treatment efficacy in subgenomic replicons was evaluated.

Main Results:

GSK2818713 exhibits enhanced activity against genotype 1a and 1b NS5A variants compared to DCV.
It shows improved activity against chimeric replicons from HCV genotypes 2-6.
Potent and durable reduction of HCV RNA levels was observed for genotypes 1a, 2a, and 3a.

Conclusions:

GSK2818713 possesses broad genotype coverage and potent antiviral activity.
Favorable pharmacokinetics and lack of cross-resistance support its selection as a preclinical candidate.
This discovery advances the development of next-generation HCV therapies.