Hepatitis C virus (HCV) NS5A protein supports the replication of HCV by interacting with viral and cellular proteins to form the HCV replicase complex, the micro-organelle that replicates HCV RNA, thus making it an excellent target for the discovery of anti-HCV therapeutics. Pibrentasvir is a novel and pan-genotypic HCV NS5A inhibitor with EC50 values ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6. Pibrentasvir inhibited HCV genotype 1a-H77, 1b-Con1, and 2a-JFH-1 subgenomic replicons with EC50 values of 1.8, 4.3 and 5.0 pM, respectively; EC50 values ranged between 1.4 and 2.8 pM against chimeric stable replicons containing NS5A derived from HCV genotypes 2a, 2b, 3a, 4a, 5a, and 6a. The 50% cytotoxicity concentration (CC50) value of pibrentasvir in an HCV genotype 1a replicon cell line was > 32,000,000 pM, producing an in vitro therapeutic index that exceeded 107-fold. Furthermore, pibrentasvir retained full activity against all of the genotype 1a and 1b single-position NS5A substitutions tested, except Y93H and Y93N of genotype 1a, which conferred ≤ 7-fold increase in EC50 to pibrentasvir (EC50 ≤ 5.1 pM)[3].
Pibrentasvir/哌仑他韦 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Huh-7 (genotype 1a replicon)
1.8 pM
3 days
Evaluate the antiviral activity of Pibrentasvir against HCV genotype 1a replicon, EC50 was 1.8 pM
To evaluate the inhibitory effect of Pibrentasvir on SARS-CoV-2 infection, results showed inhibition of over 90% of infection at the lowest concentration of 0.625 µM.
Viruses. 2023 Aug 30;15(9):1841.
Huh7.5 cells
0.05 nM
30 days
Evaluate the efficacy and barrier to resistance of Pibrentasvir against HCV genotypes 2a, 2b, and 2c, showing high efficiency in eradicating HCV infections in combination therapy.
Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01888-19.
Pibrentasvir/哌仑他韦 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
SARS-CoV-2 B.1.351 infection model
Intraperitoneal injection
24 mg/kg
Once daily for 4 days
To evaluate the prophylactic effect of Pibrentasvir in a SARS-CoV-2 infected mouse model, results showed no significant reduction in viral replication or weight loss.
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