Open enlarged HCV Life Cycle in new window.

HCV Drug Targets





The isolation and engineering of infectious Heptatitis C virus that can be used to study the full replication cycle has been a relatively recent realization in the field, as has the description and characterization of animal models for infection. These new systems will no doubt improve our understanding of infection in the future and could also influence our search for novel Hepatitis C drugs. Most of what we know about the hepatitis C lifecycle has been derived from cell-based replicon systems encompassing the events that take place after viral entry and before the formation of infectious virions. These replicons encode the non-structural portion of the hepatitis C genome and enable 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 an understanding of the full life cycle is more advanced. 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 tractable targets for antiviral drug discovery, and recent identification and clinical validation of NS5a inhibitors provides yet another avenue for drug discovery and the possibility of combination drug regimens for those patients unable to include interferon alpha as part of therapy. Further drug discovery possibilities present themselves when the strong influence and predisposition of the immune system in viral clearance is considered and non-immune host targets have also been validated in the clinic.

Our goal at Tibotec is to design potent hepatitis C therapeutic solutions with significant advantages over existing treatments, our vision is based on our belief that clearance of virus requires drug combinations. Our discovery programs are aimed at identifying drugs that;

• Suppress HCV replication and in combination result in a durable clearance of HCV infection
• Have activity against different HCV genotypes, including genotype 1
• Have a side effect and safety profile that facilitates treatment for all patients
• Tablet formulation