ABSTRACT
After the discovery of the hepatitis C virus (HCV) in 1989 (Choo et al., 1989), HCV drug development had been hampered by the absence of a robust cell culture system for HCV infection. However, a number of virologic breakthroughs have led to a new age in rational drug design for HCV infection. These include the identification of an infectious HCV sequence in chimpanzees (Kolykhalov et al., 1997), replication of subgenomic HCV RNA in a human hepatoma cell lines (Lohmann et al., 1999), HCV replication in severe combined immunodeficiency (SCID) mice with chimeric human livers (Mercer et al., 2001) and the production of infectious HCV in tissue culture from a cloned viral genome (Wakita et al., 2005). These advances in molecular biology led to a paradigm shift from traditional high-throughput drug screening toward rational, structure-based drug design for the identification of novel antiviral agents for the treatment of HCV infection (Dore et al., 2015; Pawlotsky et al. 2007).
