A hepatitis C virus NS5A inhibitor
Pibrentasvir is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with EC50s ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6.
Pibrentasvir inhibits HCV genotype 1a-H77, 1b-Con1, and 2a-JFH-1 subgenomic replicons with 50% effective concentrations (EC50s) of 1.8, 4.3, and 5.0 pM, respectively. The antiviral activity of Pibrentasvir is attenuated 35- to 47-fold in the presence of 40% human plasma through sequestration of compound due to plasma protein binding. Pibrentasvir retains full activity against all of the genotype 1a and 1b single-position NS5A substitutions tested, except Y93H and Y93N in genotype 1a, which confers a ≤7-fold increase in EC50 to Pibrentasvir[1].
[1]. Ng TI, et al. In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e02558-16.
Cell experiment: | The inhibitory effect of Pibrentasvir on HCV replication in replicon cells is determined in Dulbecco's modified Eagle's medium (DMEM) containing 5% fetal bovine serum with or without 40% human plasma. The cells are incubated with Pibrentasvir for 3 days and are subsequently lysed and processed according to the manufacturer's instructions to measure luciferase reporter activity using a Victor II luminometer. The 50% effective concentration (EC50) value is calculated using nonlinear regression curve fitting to the four-parameter logistic equation in software[1]. |
参考文献: [1]. Ng TI, et al. In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e02558-16. | |
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