Efficacy of cobalt chelates CTC-23, CTC-67, CTC-82 and CTC-96 for treatment of ocular herpes simplex infection in a rabbit model

Purpose: Herpes simplex virus (HSV) can cause corneal infections in humans that can lead to permanent scarring and loss of vision as well as blindness. The virus, after primary infection of a host, becomes senescent; recurrent disease is possible from latent virus. In this project, we use an animal model to evaluate four (4) tetradentate Co^III chelates with nitrogenous axial ligands for efficacy in treating ocular herpes. Methods: Normal 3-5 1b New Zealand White rabbits were intracorneally infected with HSV type 1, strain RE. The animals were carefully monitored until resolution of the HSV-1, then arbitrarily divided into groups receiving, for five (5) days, varying doses of: one (1) of the four (4) CTC compounds, triflurothymidine (TFT: current treatment of choice/positive control) or 0.9% physiologic saline. The animals were followed in a double-blind fashion and carefully monitored for severity/resolution of the HSV-1 via biomicroscropy (slitlamp) examination as well as viral culture techniques (ELISAs as well as plaque and infectivity assays). Results: By day 10 post-infection the lowest concentration of CTC-23 and CTC-67 administered, 5 μg/ml, had eliminated virus from the eyes of about half the animals, while at 25 μg/ml, all eyes were virus-free by day 10. CTC-96 and TFT were more effective still, eliminating virus from every eye by day 10 at both 5 and 10 μg/ml. CTC-82 had no appreciable effect upon viral titers. Conclusions: We conclude that although CTC-82 was ineffective against herpes simplex type 1, strain RE, CTC compounds 23, 67 and 96 were all effective antiviral agents.