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].
搜索
