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Y. J. Gordon, K. A. Yates, E. G. Romanowski, D. W. Stroman; Topical N,N-dichloro-2,2-dimethyltaurine (AL-46383A) Inhibits Adenovirus Replication in the Ocular Ad5/NZW Rabbit Replication Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6341.
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Presently, there is no FDA approved antiviral therapy for the treatment of adenovirus (Ad) ocular infections. N,N-dichloro-2,2-dimethyltaurine, (AL-46383A), a stable dichlorotaurine derivative, represents a new class of broad spectrum antimicrobials, the aganocides. The goal of the current study was to determine the antiviral efficacy of topical AL-46383A on acute Ad replication in the ocular Ad5/NZW rabbit replication model.
In a series of experiments, the efficacy of AL-46383A was evaluated in vivo. NZW rabbits were topically inoculated in both eyes with 1.5 x 106 pfu/eye of Ad5. On day 1, the rabbits were divided into 3 topical treatment groups: I - Vehicle Control (CON) OU 8x/day for 10 days (N=40), II - 0.3% AL-46383A (AL) OU 8x/day for 10 days (N=30), and III - 0.5% Cidofovir (CDV) OU 2x/day for 7 days (N=38). Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. The experiments were combined for statistical analysis. (Abbreviations: Ad+ Cult/Tot = Ad Positive Cultures per Total; Dur of Shed (D) = Duration of Shedding in Days).
______Ad+ Cult/Tot_____Ad+ Cult/Tot____Dur of Shed (D)______(Days 1-14)______(Days 7-14)_____Mean____Median CON__ 474/640 (74%)___59/320 (50%)___9.1±0.3____9.0AL____317/480 (66%)*___90/240 (37%)*__8.1±0.3*___7.0*CDV__280/600 (47%)#___37/296 (12%)#__5.8±0.3#___5.0#* P ≤ 0.05 Compared with Control;# P ≤ 0.05 Compared with AL-46383A and Control.AL-46383A demonstrated minimal ocular toxicity.
AL-46383A demonstrated significant anti-adenoviral activity in the Ad5/NZW rabbit ocular model. Unlike cidofovir, there was no significant toxicity (lacrimal blockade) with AL-4638A. AL-46383A is currently under investigation in a masked, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT00901693) as a topical therapy for viral conjunctivitis.
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