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, 13, 2565-2577

Glecaprevir/pibrentasvir for the Treatment of Chronic Hepatitis C: Design, Development, and Place in Therapy


Glecaprevir/pibrentasvir for the Treatment of Chronic Hepatitis C: Design, Development, and Place in Therapy

Thomas G Cotter et al. Drug Des Devel Ther.


Direct-acting antiviral (DAA) therapy has changed the landscape of hepatitis C virus (HCV) management and has changed the focus to the possibility of HCV elimination in the near future. Glecaprevir, an NS3/4A protease inhibitor, and pibrentasvir, an HCV NS5A inhibitor, have addressed many of the existing shortcomings in the DAA therapy spectrum. This combination has proven to be a highly efficacious pan-genotypic DAA with a high barrier to resistance as a once-daily, all-oral medication. This review explores the design and development of glecaprevir and pibrentasvir, its place in current HCV management in the midst of a myriad of DAA therapy options, and also remaining challenges.

Keywords: direct-acting antiviral therapy; glecaprevir; hepatitis C virus; pibrentasvir.

Conflict of interest statement

Dr Donald M Jensen reports grants from Abbvie, during the conduct of the study; received travel reimbursements from AASLD for attending annual meetings and visiting industry clients, outside the submitted work. The authors report no other conflicts of interest in this work.


Figure 1
Figure 1
Classification of hepatitis C virus into 7 major genotypes and subtypes. The tree is based on phylogenetic analysis of the open-reading frame (nucleotide) sequences. The overall prevalence and distribution are indicated for each major genotype. Note: Reprinted from Journal of Hepatology, 65, Bukh J, The history of hepatitis C virus (HCV): basic research reveals unique features in phylogeny, evolution and the viral life cycle with new perspectives for epidemic control, S2–S21, Copyright (2016), with permission from Elsevier. Abbreviations: HCV, hepatitis C virus; IDU, intravenous drug use.
Figure 2
Figure 2
The structure and replication cycle of the hepatitis C virus. The identification of the nonstructural proteins was an important therapeutic breakthrough. The sites of action of glecaprevir and pibrentasvir are shown. Abbreviations: IRES, internal ribosome entry site; E, envelope; NS, nonstructural.
Figure 3
Figure 3
The chemical structure of glecaprevir (C38H46F4N6O9S).
Figure 4
Figure 4
The chemical structure of pibrentasvir (C57H65F5N10).

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