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Hepatitis C virus (HCV) - Future HCV Drug Discovery Technologies


Description: The main hindrance to drug development for hepatitis C has been the lack of a small animal model or productive tissue culture system for assessing drug action. This problem has been addressed both by academic groups and private companies, which has resulted in a drastic improvement of the possibilities for in vivo research. The main obstacle has clearly been difficulty of achieving viral replication in the laboratory both in cell culture and animal models. A general opinion among the scientific community is that substantial hurdles still remain. Getting a reliable system to evaluate products before they go into clinical trials is very problematic. This is about to change. Several groups are now generating models with a possible ability to revolutionize HCV drug discovery. Merck is one company with a high activity in this field, working with bioinformatic tools, cellular assays and animal models. Merck’s groups at Istituto di Ricerche di Biologia (Irbm) in Italy are using several approaches to solving the HCV problem. In one project, Merck is utilizing the contribution of computational techniques and the use of structural information for the design and discovery of novel therapeutic agents for HCV. The company’s interests lie in drug discovery as well as in vaccine design. In this highlight report, we focus on describing and assessing the ongoing struggle for improved and novel HCV drug discovery technologies. Technological breakthroughs have been made and BioSeeker Group has identified improvements for new drug discovery platforms that have the potential to substantially improve HTS. Our Highlight Reports are produced to enable our customers to be updated on the progress within different sectors of the biotechnology industry, and will give you access to achievements and novel breakthroughs during the latest years of activities. Apart from the pharma industry itself, this report is of value to investors, science incubators, investigators, contract research organizations or any other types of organization with an interest in drug discovery related to infectious diseases. Companies included in the report: Agouron Pharma, Anadys Pharmaceuticals, Apath LLC, Bristol-Myers Squibb, Chiron, Chugai Pharmaceutical Company, Eli Lilly, HepaTech, Hybrigenics, ICN Pharmaceuticals, Immusol, Merck and Co., OncoImmunin, Inc., Panvera, Pfizer, Progenics, Stemcells Inc., Sumitomo Pharma, Vertex Pharm., Virogenomics Inc., XTL Biopharmaceuticals Ltd


Contents:



































































EXECUTIVE SUMMARY

3


METHODOLOGY

5


INTRODUCTION

6


IDENTIFYING HCV TARGETS UTILIZING BIOINFORMATICS

8


Artificial Neural Networks

8


Proteomics

8


Genetic and Genomic Approaches

10


Using Inverse Genomics in HCV Drug Discovery

12


DEVELOPMENT OF HCV HELICASE ASSAY

13


CELL-BASED MODELS FOR EVALUATING AGENTS AGAINST HEPATITIS C

15


A Method for Identification of Molecules Specifically Blocking HCV Translation

15


Cell-based Viral RNA Replication Systems

16


HTS Cell-based Small Molecule Inhibitor Assays for Hepatitis C Virus

16


A Cell-based Membrane Fusion Assay Measuring HCV Entry

22


Development of a Tissue Culture System to Produce High-titer HCV Pseudotype Viruses

22


WHEN WILL NEW ANIMAL MODELS BE AVAILABLE?

24


Surrogate Animal Models

24


Human-Mice Chimeric Models

25


Using Stem-Cells

26


Transgenic Models

27


CONCLUSION

28


INDEX

33




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