2004 OMIG, Abstract 1, The Charles T. Campbell Eye Microbiology Lab, UPMC | University of Pittsburgh Medical Center, Pittsburgh, PA, USA

A Novel Topical Antiviral Agent, PCL-016 (Picolinic Acid), Inhibits Adenovirus Replication in the Ad5/NZW Rabbit Ocular Model
EG Romanowski, KA Yates, RP Kowalski, FS Mah, YJ Gordon. The Charles T. Campbell Laboratory, University of Pittsburgh, Pittsburgh, PA

Purpose: The need for an effective antiviral to treat adenovirus (Ad) ocular infections persists. The goal of the current study was to determine the antiviral efficacy of a novel topical antiviral agent, PCL-016 (PCL, Picolinic Acid) a pyridine carboxylate that binds with the zinc associated with Zinc Finger Proteins to affect their structure and function, on acute adenovirus(Ad) replication in the Ad5/NZW rabbit ocular model.
Methods: 25 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 6 topical treatment groups: I - 1.5% PCL pH 7.0 (n=4); II - 0.8% PCL pH 7.0 (n=4); III - 0.369% PCL pH 7.0 (n=4); IV - 0.369% PCL pH 4.0 (n=4); V - 0.5% Cidofovir (CDV) (n=4); VI - Control (saline) (n=5). PCL and Control rabbits
were treated QID x 7 days, while CDV rabbits were treated BID x 7 days. All eyes were cultured for virus on days 0, 1,3, 4, 5, 7, 9, 11, and 14.

Results:
Group	Ad + Cultures/Total (Days 1-14)	Duration of Ad Shedding (Days)
1.5% PCL	30/64 (47%)*	5.9 ± 3.6*
0.8% PCL	31/64 (48%)*	7.0 ± 3.5*
0.369% PCL (pH7)	32/64 (50%)*	8.6 ± 4.4*
0.369% PCL (pH4)	33/64(52%)*	9.1 ± 2.5**
0.5% CDV	25/64(39%)*	5.8 ± 2.9*
Control	64/80(84%)	12.3 ± 1.9
p < 0.001 compared to the Control. *p = 0.001 compared to CDV.

Conclusions: Topical 1.5% PCL, 0.8% PCL, 0.369% PCL (pH7), 0.369% PCL (pH4) and 0.5% CDV were significantly more effective than the Control in reducing Ad Positive Cultures/Total (Days 1-14) and the Duration of Ad Shedding in the Ad5/NZW rabbit ocular model. Although not statistically significant, there appears to be concentration-dependent efficacy of PCL on the Duration of Ad Shedding. There was no apparent ocular toxicity associated with PCL concentrations. Additional studies of PCL in the experimental Ad5/NZW ocular model are indicated.