Challenges and successes in developing new therapies for hepatitis C

@article{Francesco2005ChallengesAS,
  title={Challenges and successes in developing new therapies for hepatitis C},
  author={Raffaele De Francesco and Giovanni C. Migliaccio},
  journal={Nature},
  year={2005},
  volume={436},
  pages={953-960}
}
Hepatitis C virus (HCV) will continue to be a serious global health threat for many years to come because of the chronic nature of the infection, its high prevalence and the significant morbidity of the resulting disease. Recently, a small number of molecules have produced encouraging results in proof-of-concept clinical trials. At the same time, preclinical evidence is accumulating that development of resistance will eventually limit the efficacy of new drugs. Thus, combinations of multiple… 
Replication of hepatitis C virus
TLDR
The development of complete cell-culture systems should now enable the systematic dissection of the entire viral lifecycle, providing insights into the hitherto difficult-to-study early and late steps.
The way forward in HCV treatment — finding the right path
TLDR
The specific challenges posed by HCV are reviewed, and recent developments in the design of vaccines and novel antiviral agents are reviewed.
New therapeutic options for hepatitis C
TLDR
Although many of the agents reviewed are in the early stages of development they show great promise and the ever-increasing understanding of hepatitis C virus will undoubtedly lead to exploration of new targets.
Novel interferons for treatment of hepatitis C virus.
Emerging host cell targets for hepatitis C therapy.
Therapeutic vaccines against the hepatitis C virus in the age of direct-acting antivirals
TLDR
Hepatitis C is a significant health problem worldwide, with incidence estimates around 160 million people and 500 000 annual deaths and new treatments, such as therapeutic vaccines, have arisen as additional or combined therapies against chronic HCV infection.
New advances in the molecular biology of hepatitis C virus infection: towards the identification of new treatment targets
Hepatitis C virus (HCV) causes chronic infection in almost 2% of the world's population. If untreated, chronic carriers can develop severe liver disease including fibrosis, cirrhosis and
...
...

References

SHOWING 1-10 OF 98 REFERENCES
Inhibitors of the HCV NS5B polymerase: new hope for the treatment of hepatitis C infections.
TLDR
This review provides a comprehensive account of the progress made towards the discovery of anti-HCV therapeutics based on inhibition of the virally encoded NS5B polymerase, providing validation of the approach for antiviral therapy.
An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus
TLDR
Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor, illustrating the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics.
Review HCV Antiviral Resistance: The Impact of in vitro Studies on the Development of Antiviral Agents Targeting the Viral NS5B Polymerase
TLDR
HCV sub-genomic replicons have been used to study viral resistance to both nucleoside and non-nucleoside NS5B inhibitors and suggest that drug-resistant viruses are likely to evolve in vivo.
“Strong reasons make strong actions” — The antiviral efficacy of NS3/4A protease inhibitors
TLDR
Pre‐clinical toxicology data and studies in healthy volunteers supported the administration of BILN 2061 to patients with HCV infection.
Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients.
TLDR
BILN 2061 is a well-tolerated and very active compound that reduced serum viral RNA concentrations after 2 days of treatment in patients infected with genotype 1 HCV independent of the degree of fibrosis.
In Vitro Resistance Studies of Hepatitis C Virus Serine Protease Inhibitors, VX-950 and BILN 2061
TLDR
In vitro resistance studies using a subgenomic replicon system to compare VX-950 with another HCV NS3·4A protease inhibitor, BILN 2061, are described and modeling analysis suggests that there are different mechanisms of resistance to V X-950 and BILn 2061.
Mutations Conferring Resistance to a Potent Hepatitis C Virus Serine Protease Inhibitor In Vitro
TLDR
Findings from the in vitro passage of HCV genotype 1b replicon cells in the presence of a fixed concentration of BILN 2061 provide a strategic guide for the development of next-generation inhibitors ofHCV NS3/NS4A serine protease.
Past, present, and future hepatitis C treatments.
  • G. Foster
  • Biology, Medicine
    Seminars in liver disease
  • 2004
TLDR
Pegylated interferons have improved pharmacokinetic profiles, may be administered once weekly, and are more effective than IFN is alone or in combination with ribavirin, and improves health-related quality of life during therapy compared with IFN-based therapy.
Interference of hepatitis C virus RNA replication by short interfering RNAs
TLDR
It is shown that RNAi can specifically inhibit HCV RNA replication and protein expression in Huh-7 cells that stably replicate the HCV genome, and that this antiviral effect is independent of IFN.
...
...