The therapeutic approaches for hepatitis C virus

Protease inhibitors and polymerase inhibitors

Paul Y. Kwo, Rakesh Vinayek

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The current standard of care for hepatitis C infection is peginterferon/ribavirin (PegIFN/RBV). We are entering the era where direct-acting antiviral agents (DAAs) will be added to PegIFN/RBV, leading to higher sustained response rates in genotype 1 infected individuals. Currently DAAs are directed toward specific proteins involved in hepatitis C replication with NS3/NS4A protease inhibitors furthest in development. Telaprevir and boceprevir are both NS3/NS4a inhibitors that significantly improve sustained response when added to PegIFN and RBV. The hepatitis C virus (HCV) polymerase inhibitors are another promising DAA class. These molecules are divided into nucleoside/nucleotide polymerase inhibitors and nonnucleotide/nucleoside polymerase inhibitors. Nucleoside/nucleotide polymerase inhibitors have a high barrier to resistance and appear to be effective across a broad range of genotypes. Nonnucleoside polymerase inhibitors have a lower barrier of resistance and appear to be genotype specific. Preliminary data with these compounds are also promising. A third class, NS5A inhibitors, has also shown potent HCV RNA suppression in preliminary studies as monotherapy and with PegIFN and RBV. Combinations of these agents are also entering clinical trials and indeed a preliminary report has demonstrated that the combination of an NS3/4A protease inhibitor and NS5B polymerase inhibitor can effectively suppress virus in genotype 1 individuals. Future studies will concentrate on combinations of direct-acting antiviral agents without and with PegIFN and RBV. Clinicians will need to be familiar with managing side effects as well as resistance as we enter this new era.

Original languageEnglish
Pages (from-to)406-417
Number of pages12
JournalGut and Liver
Volume5
Issue number4
DOIs
StatePublished - Dec 2011

Fingerprint

Protease Inhibitors
Hepacivirus
Antiviral Agents
Genotype
Nucleosides
Ribavirin
Hepatitis C
Nucleotides
Therapeutics
Standard of Care
Clinical Trials
RNA
Viruses
Infection
Proteins

Keywords

  • Hepatitis C virus
  • Polymerase inhibitor
  • Protease inhibitor

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

The therapeutic approaches for hepatitis C virus : Protease inhibitors and polymerase inhibitors. / Kwo, Paul Y.; Vinayek, Rakesh.

In: Gut and Liver, Vol. 5, No. 4, 12.2011, p. 406-417.

Research output: Contribution to journalArticle

Kwo, Paul Y. ; Vinayek, Rakesh. / The therapeutic approaches for hepatitis C virus : Protease inhibitors and polymerase inhibitors. In: Gut and Liver. 2011 ; Vol. 5, No. 4. pp. 406-417.
@article{f1008523b1424aa0a0a2f476961d0880,
title = "The therapeutic approaches for hepatitis C virus: Protease inhibitors and polymerase inhibitors",
abstract = "The current standard of care for hepatitis C infection is peginterferon/ribavirin (PegIFN/RBV). We are entering the era where direct-acting antiviral agents (DAAs) will be added to PegIFN/RBV, leading to higher sustained response rates in genotype 1 infected individuals. Currently DAAs are directed toward specific proteins involved in hepatitis C replication with NS3/NS4A protease inhibitors furthest in development. Telaprevir and boceprevir are both NS3/NS4a inhibitors that significantly improve sustained response when added to PegIFN and RBV. The hepatitis C virus (HCV) polymerase inhibitors are another promising DAA class. These molecules are divided into nucleoside/nucleotide polymerase inhibitors and nonnucleotide/nucleoside polymerase inhibitors. Nucleoside/nucleotide polymerase inhibitors have a high barrier to resistance and appear to be effective across a broad range of genotypes. Nonnucleoside polymerase inhibitors have a lower barrier of resistance and appear to be genotype specific. Preliminary data with these compounds are also promising. A third class, NS5A inhibitors, has also shown potent HCV RNA suppression in preliminary studies as monotherapy and with PegIFN and RBV. Combinations of these agents are also entering clinical trials and indeed a preliminary report has demonstrated that the combination of an NS3/4A protease inhibitor and NS5B polymerase inhibitor can effectively suppress virus in genotype 1 individuals. Future studies will concentrate on combinations of direct-acting antiviral agents without and with PegIFN and RBV. Clinicians will need to be familiar with managing side effects as well as resistance as we enter this new era.",
keywords = "Hepatitis C virus, Polymerase inhibitor, Protease inhibitor",
author = "Kwo, {Paul Y.} and Rakesh Vinayek",
year = "2011",
month = "12",
doi = "10.5009/gnl.2011.5.4.406",
language = "English",
volume = "5",
pages = "406--417",
journal = "Gut and Liver",
issn = "1976-2283",
publisher = "Joe Bok Chung",
number = "4",

}

TY - JOUR

T1 - The therapeutic approaches for hepatitis C virus

T2 - Protease inhibitors and polymerase inhibitors

AU - Kwo, Paul Y.

AU - Vinayek, Rakesh

PY - 2011/12

Y1 - 2011/12

N2 - The current standard of care for hepatitis C infection is peginterferon/ribavirin (PegIFN/RBV). We are entering the era where direct-acting antiviral agents (DAAs) will be added to PegIFN/RBV, leading to higher sustained response rates in genotype 1 infected individuals. Currently DAAs are directed toward specific proteins involved in hepatitis C replication with NS3/NS4A protease inhibitors furthest in development. Telaprevir and boceprevir are both NS3/NS4a inhibitors that significantly improve sustained response when added to PegIFN and RBV. The hepatitis C virus (HCV) polymerase inhibitors are another promising DAA class. These molecules are divided into nucleoside/nucleotide polymerase inhibitors and nonnucleotide/nucleoside polymerase inhibitors. Nucleoside/nucleotide polymerase inhibitors have a high barrier to resistance and appear to be effective across a broad range of genotypes. Nonnucleoside polymerase inhibitors have a lower barrier of resistance and appear to be genotype specific. Preliminary data with these compounds are also promising. A third class, NS5A inhibitors, has also shown potent HCV RNA suppression in preliminary studies as monotherapy and with PegIFN and RBV. Combinations of these agents are also entering clinical trials and indeed a preliminary report has demonstrated that the combination of an NS3/4A protease inhibitor and NS5B polymerase inhibitor can effectively suppress virus in genotype 1 individuals. Future studies will concentrate on combinations of direct-acting antiviral agents without and with PegIFN and RBV. Clinicians will need to be familiar with managing side effects as well as resistance as we enter this new era.

AB - The current standard of care for hepatitis C infection is peginterferon/ribavirin (PegIFN/RBV). We are entering the era where direct-acting antiviral agents (DAAs) will be added to PegIFN/RBV, leading to higher sustained response rates in genotype 1 infected individuals. Currently DAAs are directed toward specific proteins involved in hepatitis C replication with NS3/NS4A protease inhibitors furthest in development. Telaprevir and boceprevir are both NS3/NS4a inhibitors that significantly improve sustained response when added to PegIFN and RBV. The hepatitis C virus (HCV) polymerase inhibitors are another promising DAA class. These molecules are divided into nucleoside/nucleotide polymerase inhibitors and nonnucleotide/nucleoside polymerase inhibitors. Nucleoside/nucleotide polymerase inhibitors have a high barrier to resistance and appear to be effective across a broad range of genotypes. Nonnucleoside polymerase inhibitors have a lower barrier of resistance and appear to be genotype specific. Preliminary data with these compounds are also promising. A third class, NS5A inhibitors, has also shown potent HCV RNA suppression in preliminary studies as monotherapy and with PegIFN and RBV. Combinations of these agents are also entering clinical trials and indeed a preliminary report has demonstrated that the combination of an NS3/4A protease inhibitor and NS5B polymerase inhibitor can effectively suppress virus in genotype 1 individuals. Future studies will concentrate on combinations of direct-acting antiviral agents without and with PegIFN and RBV. Clinicians will need to be familiar with managing side effects as well as resistance as we enter this new era.

KW - Hepatitis C virus

KW - Polymerase inhibitor

KW - Protease inhibitor

UR - http://www.scopus.com/inward/record.url?scp=81855220325&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81855220325&partnerID=8YFLogxK

U2 - 10.5009/gnl.2011.5.4.406

DO - 10.5009/gnl.2011.5.4.406

M3 - Article

VL - 5

SP - 406

EP - 417

JO - Gut and Liver

JF - Gut and Liver

SN - 1976-2283

IS - 4

ER -