HSV-l is the major infectious cause of corneal blindness in the United States. Redox has synthesized transition metal complexes (CTC compounds) exhibiting potent in vitro activity against herpes group viruses. Significantly, the mode of action of these novel compounds differs from currently available antiviral nucleoside analogs. One CTC compound exhibits pronounced efficacy in the topical therapy of HSV-1-induced stromal disease in the rabbit eye. The chemical rationale for the synthesis of CTC compounds, coupled with preliminary biological activity analyses, suggests that other CTC modified complexes with active group substituents may demonstrate enhanced efficacy in topical therapy treatment of stromal disease. Phase I research identifies leading CTC compounds (3--5 chemically- engineered, biologically-active compounds) and evaluates effects of these compounds in vitro and in vivo on HSV-1 recovery and clinical progression of ocular HSV-1 stromal disease development and epithelial keratitis in rabbits. Phase II includes selection of 1 or 2 leading CTC compounds for further development as single-agent therapy against HSV-l induced ocular stromal disease in the rabbit. Additionally, in Phase II in vitro studies will investigate the mechanism of CTC antiviral activity at functional (protein products) and other molecular targets in HSV infected cells.
