Related Experiment Video
Updated: Jun 21, 2026

A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
Optimization of thienopyrrole-based finger-loop inhibitors of the hepatitis C virus NS5B polymerase
Jose Ignacio Martin Hernando1, Jesus Maria Ontoria, Savina Malancona
1Department of Medicinal Chemistry, Istituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A. Merck Sharp & Dohme Research Laboratories Rome, Via Pontina km 30,600, 00040 Pomezia (Italy).
Abstract:
Infections caused by the hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The NS5B polymerase of HCV is responsible for the replication of viral RNA and has been a prime target in the search for novel treatment options. We had discovered allosteric finger-loop inhibitors based on a thieno[3,2-b]pyrrole scaffold as an alternative to the related indole inhibitors. Optimization of the thienopyrrole series led to several N-acetamides with submicromolar potency in the cell-based replicon assay, but they lacked oral bioavailability in rats. By linking the N4-position to the ortho-position of the C5-aryl group, we were able to identify the tetracyclic thienopyrrole 40, which displayed a favorable pharmacokinetic profile in rats and dogs and is equipotent with recently disclosed finger-loop inhibitors based on an indole scaffold.
More Related Videos
11:34A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Related Concept Videos
Antiviral Nucleoside Inhibitors
Inhibitors of Viral Protein Synthesis
Inhibitors Of Virion Release
Inhibitors of Bacterial DNA Synthesis
Inhibitors of Virion Maturation and Assembly
Hepatitis