2008 OMIG, Abstract 22

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Cyclopentenylcytosine (CPE-C) Inhibits Adenovirus Replication in the Ad5/NZW Rabbit Ocular Model.
EG Romanowski, KA Yates, YJ Gordon
The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
 
Purpose. Presently, there is no FDA approved antiviral therapy for the treatment of adenovirus (Ad) ocular infections. The goal of the current study was to determine the antiviral efficacy of topical Cyclopentenylcytosine (CPE-C), a nucleoside analog of cytosine, on acute Ad replication in the Ad5/NZW rabbit ocular model.
Methods. 40 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 4 topical treatment groups (n=10/group): I - 3% CPE-C, QID x 7 days; II - 3% CPE-C, BID x 7 days; III - 0.5% Cidofovir (CDV), BID x 7 days; IV - Control (saline), QID x 7 days. Both eyes of the rabbits were similarly treated. All eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14.
Results.
                    Ad5 + Cultures/Total    Duration of Ad5     Mean Ad5 Titer    Mean Ad5 Titer
Group                  (Days 1-14)                Shedding (Days)     (Days 1-5)                  (Days 7-14)     
CPE-C (QID)    24/160 (15%)*       1.3 ± 1.6*                  3.5 ± 18.1 x 101*    3.6 ± 25.2 x 100* 
CPE-C (BID)    31/160 (19%)*        2.5 ± 2.3*                 1.6 ± 4.8 x 101*      1.0 ± 4.4 x 100* 
CDV                    27/160 (17%)*        2.0 ± 1.8*       6.7 ± 12.7 x 100*    0.3 ± 2.2 x 100* 
Control              97/160 (61%)          8.1 ± 3.5                   1.0 ± 3.0 x 102        2.2 ± 9.2 x 101 
* p < 0.011 compared to the Control.

Topical 3% CPE-C four times daily and twice daily and 0.5% Cidofovir twice daily were significantly more effective than the Control in reducing Ad5 Positive Cultures/Total (Days 1-14), Duration of Ad5 Shedding, Mean Ad5 Titer (Days 1-5), and Mean Ad5 Titer (Days 7-14) in the Ad5/NZW rabbit ocular model. There were no significant differences between the two topical regimens of 3% CPE-C and both were as effective as the positive antiviral control, 0.5% Cidofovir.
Conclusions. CPE-C demonstrated potent anti-adenoviral activity in the Ad5/NZW rabbit ocular model. Additional studies are warranted to establish the clinical potential of CPE-C as a topical antiviral treatment for adenovirus ocular infections.

Disclosure Code: None     
Support: NIH Grant EY08227 (YJG), NIH Core Grant EY08098 (OVSRC), Eye & Ear Foundation of Pittsburgh, RPB.