ASP 2151

Amenamevir is an antiviral inhibitor of herpes simplex virus 1 (HSV-1) helicase-primase complex activity. It inhibits recombinant HSV-1 helicase with an IC₅₀ value of 0.078 μM and recombinant HSV-1 primase when used at concentrations greater than or equal to 0.03 μM. Amenamevir inhibits replication of varicella-zoster virus (VZV), HSV-1, and HSV-2 in human embryonic fibroblast (HEF) cells (EC₅₀s = 0.047, 0.036, and 0.028 μM, respectively) and is not cytotoxic to HEF cells with a 50% cytotoxic concentration (CC₅₀) of greater than 30 μM. Amenamevir also inhibits replication of clinical VZV isolates in HEF cells (EC₅₀s = 0.038-0.10 μM). In vivo, it increases survival of cutaneously HSV-1-infected mice in a zosteriform-spread model of progressive HSV-1 infection (ED₅₀ = 1.9 mg/kg twice per day).