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K.A. Yates, E.G. Romanowski, B. Teuchner, M. Nagl, W. Gottardi, Y.J. Gordon; Topical N–Chlorotaurine (NCT), an Endogenous Microbicidal Oxidant, Inhibits Adenovirus Replication in the Ad5/NZW Rabbit Ocular Model . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1025.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: N–chlorotaurine (NCT), an endogenous microbicidal oxidant produced by stimulated human leukocytes, has broad spectrum antimicrobial activity against bacteria, virus, fungi and parasites. NCT demonstrated no ocular toxicity in Phase 1 clinical trials. NCT demonstrated concentration–dependent direct inactivation of multiple ocular adenovirus (Ad) serotypes in vitro (ARVO 2002). In the current in vivo study, we determined the antiviral effect of topical NCT on acute Ad replication in the Ad5/NZW rabbit ocular model. Methods: 50 NZW rabbits were topically inoculated in both eyes, following corneal scarification, with 1.5 x 106 pfu/eye of Ad5. On day 1, the rabbits were divided into 5 topical treatment groups containing 10 rabbits each: I – 2.5% NCT; II – 2.0% NCT; III – 1.0% NCT; IV – 0.5% Cidofovir (CDV); V – Control (saline). NCT and Control rabbits were treated in both eyes 10 times daily for 1 day and 5 times daily for 6 days, while CDV rabbits were treated in both eyes twice daily for 7 days. All eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Results: 2.5% NCT (74/159, 46.5%), 2.0% NCT (75/152, 49.3%), 1.0% NCT (82/152, 53.9%), and 0.5% CDV (67/160, 41.9%) demonstrated significantly fewer Positive Cultures per Total Days 1–14 compared with the Control (115/160, 71.9%) (p < 0.001, Chi–square). On a daily basis, 2.5% NCT (Days 1, 4, 5, 7), 2.0% NCT (Days 1, 4, 5), 1.0% NCT (Day 1, 4, 5), and 0.5% CDV (Day 4, 5, 7) all demonstrated significantly fewer Positive Cultures per Total compared with the Control (p < 0.035, Chi–square). Conclusions: Topical NCT appears to be a promising candidate as a broad spectrum topical antimicrobial. Additional studies to evaluate the antiviral properties of NCT in the experimental Ad5/NZW ocular model are indicated.
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