Hepatitis C virus (HCV) is an enveloped, single-stranded, positive-sense RNA virus in the Flaviviridae family. The serine protease encoded by the HCV NS3 and NS4A genes is an attractive target for the discovery of direct-acting antivirals (DAAs). Glecaprevir is a novel HCV NS3/4A protease inhibitor (PI) with pangenotypic activity. It inhibited the enzymatic activity of purified NS3/4A proteases from HCV genotypes 1 to 6 in vitro (IC50 = 3.5 to 11.3 nM) and the replication of stable HCV subgenomic replicons containing proteases from genotypes 1 to 6 (EC50 = 0.21 to 4.6 nM). Glecaprevir had a median EC50 of 0.30 nM (range, 0.05 to 3.8 nM) for HCV replicons containing proteases from 40 samples from patients infected with HCV genotypes 1 to 5. Of note, glecaprevir was active against a replicon containing the protease from genotype 3, the most-difficult-to-treat HCV genotype, with an EC50 of 1.9 nM[3]. Genotype 3-infected patients who were treated for 12 weeks had a rate of sustained virologic response at 12 weeks of 95% (95% CI, 93 to 98; 222 of 233 patients) with once-daily glecaprevir-pibrentasvir (a direct-acting antiviral agent)[4].
Glecaprevir/格来普韦 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A549-hACE2 cells
>94 µM
46 to 50 hours
Evaluate the inhibitory effect of Glecaprevir on SARS-CoV-2 in A549-hACE2 cells, no EC50 was determined due to antiviral activity of DMSO at high inhibitor concentrations
Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0268020.
Vero E6 cells
>178 µM
46 to 50 hours
Evaluate the inhibitory effect of Glecaprevir on SARS-CoV-2, results showed low potency
Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0268020.
MDCK cells
0.1, 1, 10, 100 µM
48 hours
Evaluate the cytotoxicity and antiviral activity of Glecaprevir on MDCK cells. Results showed that Glecaprevir significantly reduced cell activity at 100 µM concentration with a CC50 of 77.32 µM.
Int J Mol Sci. 2025 Feb 6;26(3):1381.
MT4 cells
59,000 nM
Evaluation of cytotoxicity of Glecaprevir in MT4 cells
Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01620-17.
HepG2 cells
62,000 nM
Evaluation of cytotoxicity of Glecaprevir in HepG2 cells
Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01620-17.
Huh-7 cells
0.21 to 4.6 nM
Evaluation of antiviral activity of Glecaprevir against HCV replicons of different genotypes
Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01620-17.
Glecaprevir/格来普韦 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c mice
H1N1-UI182 influenza virus infection model
Oral
10, 20, 40 mg/kg
Once daily for 14 days
Evaluate the therapeutic effect of Glecaprevir on H1N1-UI182 influenza virus-infected mice. Results showed that Glecaprevir significantly improved the survival rate of infected mice (80% protection rate) and alleviated lung pathological damage.
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