A Novel Topical Antiviral Agent, PCL–016 (Picolinic Acid), Inhibits Adenovirus Replication in the Ad5/NZW Rabbit Ocular Model

Abstract

 

Abstract:

 

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) on acute Ad replication in the Ad5/NZW rabbit ocular model. PCL–016, a pyridine carboxylate, acts by binding with the zinc associated with Zinc Finger Proteins to alter their structure and inhibit function.

 

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 in both eyes 4 times daily for 7 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.

 

 

 

^{* p < 0.001 compared to the Control. p = 0.001 compared to CDV.}

 

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 a trend toward 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.

 

 

Keywords: adenovirus • antiviral drugs • conjunctivitis