The difficulties in growing HCV in cell culture have impeded the study of the viral life cycle as well as the development of specific antiviral agents and vaccines. The development of cell-based replicon systems has provided tools for elucidating at least some parts of the viral lifecycle. These systems also facilitated drug screening programs aimed at targeting proteins involved in HCV RNA replication and polypeptide processing. The processes of HCV viral entry and virion production depicted in the Figure are modeled on those of other (+) strand RNA viruses where the full life cycle has been better studied. The HCV genome encodes a polypeptide that is cleaved into 10 proteins. Several of these proteins (e.g. NS5B RNA polymerase and NS3/4A protease) have structural and enzymatic functions that make them suitable targets for antiviral therapy. An "internal ribosome entry site" in the 5' UTR region and host factors represent additional targets for drug therapy. Recently several groups have reported the production of recombinant infectious HCV in tissue culture, an advance that should enhance our ability to discover novel HCV drugs.
Our goal at Tibotec is to design potent hepatitis C therapeutics with significant advantages over the existing standard of care specifically with regard to:
Suppression of HCV replication and durable clearance of HCV infection
Activity against different HCV genotypes, including genotype 1
Side effect profile and safety
Tablet formulation
An integrated viral pharmacogenomic program provides Tibotec with a scientific basis for determining the influence of host genetic background, HCV sequence diversity and resistance potential, in the development a new generation of HCV treatments.
