HCV NS5A replication complex inhibitors

Abstract

The development of anti-HCV drugs is one of the most successful stories of antiviral therapy. In fact, for the first time in human history we have the potential to eradicate a chronic viral infection using only orally administered direct antiviral agents (DAAs). HCV NS5A replication complex inhibitors, exemplified by Daclatasvir (DCV, BMS-790052, Daklinza®), are a new class of DAA. The astonishing in vitro potency of DCV (pM to low nM range) translated to remarkable efficacy in clinical trials, and 2nd generation NS5A inhibitors have become essential components of HCV combination therapies. The current cure rate of effective combination therapies exceeds 90% in most clinical trials. The extraordinary potency of NS5A inhibitors promoted significant efforts to understand their mechanism(s) of inhibition.