Entry Inhibitors of Hepatitis C Virus

Hepatitis C virus (HCV) infection affects approximately 1% of the world's population and is a major cause of chronic liver diseases. Although antiviral therapy consisting of direct-acting antivirals (DAAs) can cure the majority of HCV patients, it is still limited by viral resistances, drug-drug interactions, and high costs. Moreover, the role of DAAs in the prevention of occurrences of graft reinfection in HCV patients who receive liver transplantations is still under comprehensive clinical investigation, bringing the risk of recipient reinfection. HCV entry is composed of initial non-specific attachment and binding, post-binding interactions with essential host factors, internalization, and virion-cell membrane fusion to release viral RNA to cytosol. Thus, a number of novel and promising targets from either virion or cellular factors of these processes become optimal interfering elements for antiviral therapy, eliminating viral infection at the very beginning. Therefore, entry inhibitors can be supplemented into the future treatment regimens to optimize and widen the prevention and therapeutics of HCV infection. This chapter introduces the basic HCV entry processes and summarizes molecular mechanisms and research status of the current antiviral agents targeting HCV entry in preclinical and clinical study.