Treatment of Hepatitis C Virus (HCV) infection is rapidly evolving with the 
introduction of direct acting antiviral agents (DAA). HCV NS5A replication 
complex inhibitors, exemplified by Daclatasvir (BMS-790052), represent a new 
class of DAA. The exceptional in vitro potency (EC50 values at pM to low nM 
range) and broad genotype coverage of NS5A inhibitors have translated to robust 
anti-HCV effects in infected patients, making NS5A inhibitors an essential 
component of effective HCV DAA combination therapies. On the basis of 
drug-induced resistance substitutions and computer modeling, NS5A inhibitors 
most likely act at the N-terminus of NS5A (domain I). Mechanism of inhibition 
studies to elucidate the exquisite potency of these inhibitors have generated 
several working models.