Mucocutaneous viral infections including human papillomavirus (HPV)-induced warts have a significant impact on the world population. HPV infections lead to cutaneous lesions, discomfort and pain, as well as associated psychosocial morbidity. Tetraethylammonium chloride (TEAC) is a known nicotinic ganglion blocker and potassium channel blocker that has demonstrated broad-spectrum in vitro antiviral activity, as well as in vivo antiviral activity in animal models, and anecdotal antiviral activity in man. TEAC's antiviral mechanism of action (MOA) is not completely understood. This proposal will explore the potential to develop marketable, topical TEAC formulations for treating papilloma-induced common warts, with the use of an animal model. The goals of this proposal are: 1) Optimize topical TEAC formulations suitable for preclinical toxicology and human clinical trials, which will be central to a future Phase II proposal, through in vitro skin permeation studies using t4C-TEAC, to monitor skin deposition and penetration parameters as a function of vehicle composition. 2) Test the efficacy of the formulations in vivo in a cottontail rabbit papillomavirus (CRPV) model; and 3) Determine the antiviral MOA for TEAC in papillomavirus-induced common warts. Specific channel blockers and an acetylcholine receptor antagonist, which represents the potential antiviral MOAs of TEAC, will be used in vivo in the CRPV model to help discern TEAC's MOA. Approximately 8% of visits to dermatologists are for non-genital warts caused by HPV. Current therapies for HPV-induced common warts are minimally effective with painful side-effects and potential systemic toxicity. TEAC is an old drug with known safety in man with reported in vitro and suspected in vivo antiviral activity. Topical TEAC should provide a safe and effective therapy for common warts with no significant side effects.
