In vitro hepatitis C virus replication systems and novel therapeutic agents for chronic hepatitis C
Ntziora F., Magiorkinis G., Hatzakis A.
Until recently, due to the lack of an effective cell culture system for the Hepatitis C Virus (HCV), the design of novel therapeutic agents was difficult. The recent progress in the molecular virology of HCV has created the appropriate conditions for the development of in vitro viral replication systems and has led to research that was previously impossible. The first viral replication systems (replicons) were subgenomic, while currently full-length replicons are available. A full-length HCV genome that replicates and produces virus particles that are infectious in cell culture (HCVcc) has allowed the study of the natural characteristics of HCV. Up until the present, recombinant Interferon (IFN) a-2a, a-2b and pegylated interferon (PEG-IFN) alone or in combination with ribavirin have been the only approved available treatments. Serious side-effects and low efficacy of the current treatments, along with high prevalence of the infection worldwide mandate that new therapeutic agents need to be developed. NS3 protease, responsible for the release of non-structural viral proteins, and RNA-dependent-RNA-polymerase (RdRp) of NS5B are potential targets. Apart from the NS protease inhibitors other compounds play a significant rote in the treatment of HCV infection, among which cyclosporin A, albuferon, merimepodib or VX-497, viramidin, arsenic trioxide (ATO), sodium stibogluconate (SSG) and interleukins 28 (IL-28) and 29 (IL-29) are examples.