The in vitro and in vivo evaluation of ddC as a topical antiviral for ocular adenovirus infections.
OBJECTIVE
To evaluate the antiviral activity of 2', 3'-dideoxycytidine (ddC) in vitro against a panel of ocular adenovirus serotypes and in vivo in the ocular Ad5/NZW rabbit replication model.


METHODS
In vitro, the 50% inhibitory concentrations (IC(50)) of ddC and cidofovir were determined using standard plaque-reduction assays. In vivo, 40 rabbits were topically inoculated in both eyes with Ad5 after corneal scarification. On day 1, the rabbits were equally divided into four topical treatment groups: 3% ddC; 2% ddC; 0.5% cidofovir; and saline. ddC and saline eyes were treated four times daily for 7 days, and cidofovir-treated eyes were treated twice daily for 7 days. Eyes were cultured for virus a multiple times over 2 weeks.


RESULTS
The in vitro IC(50) for ddC ranged from 0.18 to 1.85 microg/mL, whereas those for cidofovir ranged from 0.018 to 5.47 microg/mL. ddC was more potent than cidofovir for seven of nine serotypes. In vivo, 3% ddC, 2% ddC, and 0.5% cidofovir significantly reduced the number of Ad5-positive cultures per total (days 1-14), mean Ad5 ocular titer (days 1-5), and duration of shedding (among other outcome measures) compared with the saline control. The 3% and 2% ddC treatments were significantly more efficacious than the 0.5% cidofovir treatment in the parameters listed above.


CONCLUSIONS
ddC demonstrated potent antiadenovirus activity in vitro and in vivo. Systemic safety studies after topical ocular administration are needed to evaluate ddC as a topical antiviral treatment for adenoviral ocular infections in the target population.
Romanowski
Eric G
EG
Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. romanowskieg@upmc.edu
Yates
Kathleen A
KA
Gordon
Y Jerold
YJ
D000257:Adenoviridae Infections / Q000188:drug therapy* / Q000821:virology; D000260:Adenoviruses, Human / Q000302:isolation & purification / Q000502:physiology*; D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D000077404:Cidofovir; D003236:Conjunctivitis, Viral / Q000188:drug therapy* / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D063065:Organophosphonates / Q000494:pharmacology; D011817:Rabbits; D014407:Tumor Cells, Cultured / Q000821:virology; D010948:Viral Plaque Assay; D014779:Virus Replication; D016047:Zalcitabine / Q000008:administration & dosage*
D000998:Antiviral Agents; D063065:Organophosphonates; D016047:Zalcitabine; D003596:Cytosine; D000077404:Cidofovir