Hepatitis C virus replication and potential targets for direct-acting agents

We finally stand at the brink of novel, oral, direct-acting antivirals for the treatment of hepatitis C virus (HCV) infection. Basic science research has lead to a greater understanding of the viral life cycle and identified numerous potential targets for therapy. Early compounds were plagued by inconsistent in vivo activity and side effects that led to discontinuation of investigational efforts. However, several agents have now progressed to phase 2 human studies and two protease inhibitors have completed enrolment for their phase 3 clinical trials and look promising. Thus, while it appears that protease inhibitors will likely be the next available drugs for the treatment of HCV infection, the quest for additional therapeutic agents will continue. The future of HCV therapy lies in multidrug cocktails of several agents targeted against a variety of targets. In the near future these agents will be added to the current standard therapy consisting of pegylated interferon and ribavirin; however, the ultimate and probably realistic goal will be to develop multidrug oral regiments to replace the need for interferon.