Helicase–Primase Inhibitors as the Potential Next Generation of Highly Active Drugs Against Herpes Simplex Viruses

Abstract

Since the introduction of the nucleoside analogs decades ago, treatment of herpes simplex virus (HSV) infections has not seen much innovation, except for the development of their respective prodrugs. The inhibitors of the helicase–primase complex of HSV represent a very innovative approach to the treatment of herpesvirus disease, and this article considers the development of some representatives of this class of therapeutics. The molecular and biochemical features of the helicase–primase complex are considered and the development of three inhibitors of helicase–primase, BILS 179 BS, AIC316 and ASP2151, is described. The clinical development of AIC316 is at an advanced stage and displays general safety as well as favorable, long-lasting exposures in healthy volunteers. The first efficacy data from a Phase II trial with more than 150 HSV-2-positive subjects demonstrated dose-dependent antiviral activity.