Inhibition of HCV p7 as a therapeutic target

Abstract

Current standard-of-care therapy for HCV infection, comprising a combination of IFNalpha and ribavirin (IFN/Rib), is ineffective in more than 50% of patients, and is associated with poor patient compliance and high cost. The recent development of an infectious culture system for HCV has allowed investigators to target the complete life cycle of the virus in an attempt to develop new, virus-specific drugs. Compounds specific for classical HCV targets, such as the viral protease and polymerase, have reached phase II/III clinical trials, and encouraging results have indicated that these virus-specific compounds may complement and eventually replace therapy with IFN/Rib. However, the variable nature of HCV (quasispecies and genotype variation) and the limited number of compounds developed thus far have prompted research aimed at expanding the repertoire of available targets, resulting in processes such as virus assembly being targeted therapeutically. The viral ion channel p7 is critical for the release of HCV virions, and the sensitivity of this channel to small-molecule inhibitors renders p7 a promising target for novel therapies. Small-molecule p7 inhibitors, although at an early stage of development, block virion production in culture effectively, and limited clinical data, although controversial because of the variable antiviral effects observed, suggest that p7 inhibitors could represent effective additions to combination therapies with other virus-specific drugs.