Several potential targets have been identified within the HCV molecular structure (see Table 2 below). HCV has a protease which differs significantly from the HIV protease, but is essential during the virus life cycle. HCV also uses a helicase enzyme, which unwinds the double RNA complex as the virus copies itself. The molecular structures of these targets have been determined, and drugs to inhibit these sites are being developed. A third enzyme that is critical to HCV replication is an RNA-dependent RNA polymerase, representing another potential target for inhibition. HCV protein translation is also dependent on a unique viral region called the internal ribosomal entry site (IRES). This structure is not found in human eukaryotic cells and is homologous across all HCV genotypes, making it an excellent target for selective antivirals. Additional novel approaches, such as the development of antisense molecules, which may prevent the production of HCV proteins and degrade HCV RNA, are being pursued. However, despite aggressive research efforts, progress in the development of these new drugs is impeded by the lack of a cell or animal model that would allow rapid screening of candidate drugs. Current expectations are that some of these new drugs may be available over the next 3 to 5 years for the combination therapy of HCV infection.

Table 2. Emerging Therapies for Chronic Hepatitis C Virus Infection

Drug Class Mechanism of Action Timeline (Estimated)

Pegylated-interferon ą Ribavirin Interferon chemically bound to polyethylene glycol (PEG); allows for the slow, continuous release of interferon 1999

Helicase inhibitors Prevent unwinding of double-stranded viral RNA during HCV replication 2001-2003

Protease inhibitors Prevent cleavage of large viral protein into smaller segments 2001-2003

RNA-dependent RNA polymerase inhibitors Prevent replication or copying of the HCV genome 2001-2003

IRES (internal ribosomal entry site) inhibitors Prevent the expression of viral proteins 2001-2003

Antisense nucleotides Bind to interferon resistance sites 2008

DNA vaccines Stimulate cytotoxic T cell activity 2008

Dominant negative mutants Block viral protein production 2008

Table 2. Emerging Therapies for Chronic Hepatitis C Virus Infection
Drug Class	Mechanism of Action	Timeline (Estimated)
Pegylated-interferon ą Ribavirin	Interferon chemically bound to polyethylene glycol (PEG); allows for the slow, continuous release of interferon	1999
Helicase inhibitors	Prevent unwinding of double-stranded viral RNA during HCV replication	2001-2003
Protease inhibitors	Prevent cleavage of large viral protein into smaller segments	2001-2003
RNA-dependent RNA polymerase inhibitors	Prevent replication or copying of the HCV genome	2001-2003
IRES (internal ribosomal entry site) inhibitors	Prevent the expression of viral proteins	2001-2003
Antisense nucleotides	Bind to interferon resistance sites	2008
DNA vaccines	Stimulate cytotoxic T cell activity	2008
Dominant negative mutants	Block viral protein production	2008