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Updated: May 3, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Simeprevir: a macrocyclic HCV protease inhibitor
R Talwani1, E L Heil2, B L Gilliam1
1Institute of Human Virology and Division of Infectious Diseases, University of Maryland Medical Center, Baltimore, Maryland, USA.
Abstract:
Simeprevir is a macrocyclic NS3/4A HCV protease inhibitor with potent activity against genotypes 1, 2, 4, 5 and 6 of the hepatitis C virus (HCV). Phase II and III studies of simeprevir combined with pegylated interferon (peg-IFN) and ribavirin (RBV) demonstrated that the combination was safe and effective in HCV genotype 1 patients, with more than 75% of treatment-naive patients attaining a sustained virological response (SVR). Simeprevir is administered once daily as a single 150-mg capsule. It has a moderate drug interaction potential, but less than that of the first-generation HCV protease inhibitors. Based on positive results from the product's phase III clinical program, simeprevir was approved and launched in Japan, the U.S. and Canada in late 2013 for use in combination with peg-IFN/RBV in HCV genotype 1 infections. Phase II interferon-free studies of simeprevir are ongoing.
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