Modulation of host metabolism as a target of new antivirals

Masanori Ikeda, Nobuyuki Kato

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The therapy for chronic hepatitis C (CH-C) started with interferon (IFN) monotherapy in the early 1990s and this therapy was considered effective in about 10% of cases. The present standard therapy of pegylated IFN with ribavirin achieves a sustained virologic response in about 50% of patients. However, about half of the CH-C patients are still at risk of fatal liver cirrhosis and hepatocellular carcinoma. The other significant event in hepatitis C virus (HCV) research has been the development of a cell culture system. The subgenomic replicon system enables robust HCV RNA replication in hepatoma cells. And recently, the complete life cycle of HCV has been achieved using a genotype 2a strain, JFH1. These hallmarks have provided much information about the mechanisms of HCV replication, including information on the host molecules required for the replication. Anti-HCV reagents targeting HCV proteins have been developed, and some of them are now in clinical trials. However, the RNA-dependent RNA polymerase frequently causes mutations in the HCV genome, which lead to the emergence of drug-resistant HCV mutants. Some of the cellular proteins essential for HCV RNA replication have already been discovered using the HCV cell culture system. These host molecules are also candidate targets for antivirals. Here, we describe the recent progress regarding the anti-HCV reagents targeting host metabolism.

Original languageEnglish
Pages (from-to)1277-1289
Number of pages13
JournalAdvanced Drug Delivery Reviews
Volume59
Issue number12
DOIs
Publication statusPublished - Oct 10 2007

Fingerprint

Hepacivirus
Antiviral Agents
Virus Replication
Chronic Hepatitis C
Interferons
Hepatocellular Carcinoma
Cell Culture Techniques
RNA
RNA Replicase
Replicon
Ribavirin
Secondary Prevention
Life Cycle Stages
Liver Cirrhosis
Proteins
Genotype
Clinical Trials
Genome
Mutation
Therapeutics

Keywords

  • Antiviral
  • Hepatitis C virus
  • Host metabolism
  • Interferon
  • Replicon
  • Statin

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Modulation of host metabolism as a target of new antivirals. / Ikeda, Masanori; Kato, Nobuyuki.

In: Advanced Drug Delivery Reviews, Vol. 59, No. 12, 10.10.2007, p. 1277-1289.

Research output: Contribution to journalArticle

@article{97c1c1fa827b44f997ba61d08b202b35,
title = "Modulation of host metabolism as a target of new antivirals",
abstract = "The therapy for chronic hepatitis C (CH-C) started with interferon (IFN) monotherapy in the early 1990s and this therapy was considered effective in about 10{\%} of cases. The present standard therapy of pegylated IFN with ribavirin achieves a sustained virologic response in about 50{\%} of patients. However, about half of the CH-C patients are still at risk of fatal liver cirrhosis and hepatocellular carcinoma. The other significant event in hepatitis C virus (HCV) research has been the development of a cell culture system. The subgenomic replicon system enables robust HCV RNA replication in hepatoma cells. And recently, the complete life cycle of HCV has been achieved using a genotype 2a strain, JFH1. These hallmarks have provided much information about the mechanisms of HCV replication, including information on the host molecules required for the replication. Anti-HCV reagents targeting HCV proteins have been developed, and some of them are now in clinical trials. However, the RNA-dependent RNA polymerase frequently causes mutations in the HCV genome, which lead to the emergence of drug-resistant HCV mutants. Some of the cellular proteins essential for HCV RNA replication have already been discovered using the HCV cell culture system. These host molecules are also candidate targets for antivirals. Here, we describe the recent progress regarding the anti-HCV reagents targeting host metabolism.",
keywords = "Antiviral, Hepatitis C virus, Host metabolism, Interferon, Replicon, Statin",
author = "Masanori Ikeda and Nobuyuki Kato",
year = "2007",
month = "10",
day = "10",
doi = "10.1016/j.addr.2007.03.021",
language = "English",
volume = "59",
pages = "1277--1289",
journal = "Advanced Drug Delivery Reviews",
issn = "0169-409X",
publisher = "Elsevier",
number = "12",

}

TY - JOUR

T1 - Modulation of host metabolism as a target of new antivirals

AU - Ikeda, Masanori

AU - Kato, Nobuyuki

PY - 2007/10/10

Y1 - 2007/10/10

N2 - The therapy for chronic hepatitis C (CH-C) started with interferon (IFN) monotherapy in the early 1990s and this therapy was considered effective in about 10% of cases. The present standard therapy of pegylated IFN with ribavirin achieves a sustained virologic response in about 50% of patients. However, about half of the CH-C patients are still at risk of fatal liver cirrhosis and hepatocellular carcinoma. The other significant event in hepatitis C virus (HCV) research has been the development of a cell culture system. The subgenomic replicon system enables robust HCV RNA replication in hepatoma cells. And recently, the complete life cycle of HCV has been achieved using a genotype 2a strain, JFH1. These hallmarks have provided much information about the mechanisms of HCV replication, including information on the host molecules required for the replication. Anti-HCV reagents targeting HCV proteins have been developed, and some of them are now in clinical trials. However, the RNA-dependent RNA polymerase frequently causes mutations in the HCV genome, which lead to the emergence of drug-resistant HCV mutants. Some of the cellular proteins essential for HCV RNA replication have already been discovered using the HCV cell culture system. These host molecules are also candidate targets for antivirals. Here, we describe the recent progress regarding the anti-HCV reagents targeting host metabolism.

AB - The therapy for chronic hepatitis C (CH-C) started with interferon (IFN) monotherapy in the early 1990s and this therapy was considered effective in about 10% of cases. The present standard therapy of pegylated IFN with ribavirin achieves a sustained virologic response in about 50% of patients. However, about half of the CH-C patients are still at risk of fatal liver cirrhosis and hepatocellular carcinoma. The other significant event in hepatitis C virus (HCV) research has been the development of a cell culture system. The subgenomic replicon system enables robust HCV RNA replication in hepatoma cells. And recently, the complete life cycle of HCV has been achieved using a genotype 2a strain, JFH1. These hallmarks have provided much information about the mechanisms of HCV replication, including information on the host molecules required for the replication. Anti-HCV reagents targeting HCV proteins have been developed, and some of them are now in clinical trials. However, the RNA-dependent RNA polymerase frequently causes mutations in the HCV genome, which lead to the emergence of drug-resistant HCV mutants. Some of the cellular proteins essential for HCV RNA replication have already been discovered using the HCV cell culture system. These host molecules are also candidate targets for antivirals. Here, we describe the recent progress regarding the anti-HCV reagents targeting host metabolism.

KW - Antiviral

KW - Hepatitis C virus

KW - Host metabolism

KW - Interferon

KW - Replicon

KW - Statin

UR - http://www.scopus.com/inward/record.url?scp=35648972113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35648972113&partnerID=8YFLogxK

U2 - 10.1016/j.addr.2007.03.021

DO - 10.1016/j.addr.2007.03.021

M3 - Article

C2 - 17897752

AN - SCOPUS:35648972113

VL - 59

SP - 1277

EP - 1289

JO - Advanced Drug Delivery Reviews

JF - Advanced Drug Delivery Reviews

SN - 0169-409X

IS - 12

ER -