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2001 Ocular Microbiology and Immunology Group, Abstract 19

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Beyond Cidofovir: The In Vitro Evaluation of Potential Antiviral Agents Against Ocular Isolates of denovirus
E. G. Romanowski, K.A. Yates, and Y. J. Gordon
The Charles T. Campbell Laboratory, University of Pittsburgh, Pittsburgh, PA
Purpose: Toxicity and marketing issues following clinical trails of cidofovir, the first antiviral agent tested for the treatment of adenovirus (Ad) ocular infections, cast doubt on its further clinical development. This leaves the ophthalmic community without a safe antiviral agent to treat EKC for the forseeable future. The goal of the current study was to evaluate the antiviral inhibitory activity of five potential antiviral agents against ocular isolates of seeral serotypes of Ad in vitro and compare their inhibitory activities to cidofovir.

Methods: 6-Azacytidine (6-AZA), cyclopentenyl-cytosine (CPE-C) 2-Deoxy-d-glucose (DG) 2'4'-Dideoxycytidine (ddC), Ribavirin (RBV) and Cidofofir (CDV) were evaluated in duplicate trials for anti-adenoviral activity using a standard plaque-reduction assay on A549 cells. The antivirals were tested against clinical isolates of Ad1, Ad2, Ad4, Ad7a, Ad8, Ad19, and ATCC Ad37. The data is expressed as the mean concentration that inhibited 50% of the firus plaques (IC50) an agent with an IC50 , 120µg/ml is considered to be a potent antiviral.

IC50 [µ/ml]

Antiviral Ad1 Ad2 Ad3 Ad4 Ad5 Ad7a Ad8 Ad9 Ad37
6AZA 23.4 45.0 19.0 29.8 10.8 17.9 48.8 46.0 3.50
CPE-C 0.032 0.026 ND ND 0.028 ND 0.036 0.039 ND
2-DG >100 >100 >100 >100 >100 >100 >100 >100 >100
ddC 0.32 0.32 0.32 0.51 1.85 0.18 0.33 0.32 1.01
RBV 21.5 15.5 50.5 30.5 22.3 33.5 >100 >100 >100
CDV 2.25 2.55 0.18 1.33 3.10 5.47 0.018 4.30 1.15

ND=Not done

Conclusion: The antiviral agents CPE-C and ddC appear to be potent inhibitors of several ocular Ad serotypes in vitro while 6-AZA, 2-DG, and RBV to do not. Compared to CDV, both CPE-C and ddC appear to be more potent in vitro against most of the ocular AD serotypes tested. Further studies of the antiviral efficacy and toxicity of topical CPE-C and ddC in the Ad/NZW rabbit ocular model are warranted.

Support: NIH Grant EY05323, NIH Core Grant EY08098, Eye & Ear Foundation and RPB

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