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Eric G Romanowski, Kathleen A Yates, Robert M Q Shanks, John E Romanowski, Regis P Kowalski; OKG-0301, a Novel Ribonuclease, Demonstrates Antiviral Activity against Adenovirus in the Ad5/NZW Rabbit Ocular Model.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3614.
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© ARVO (1962-2015); The Authors (2016-present)
At present, there is no FDA approved antiviral therapy available for the treatment of adenovirus (Ad) ocular infections. OKG-0301 is a novel ribonuclease which preferentially degrades tRNA leading to an inhibition of protein synthesis. It has been previously shown to have antiviral activity against HIV. The goal of the current study was to evaluate the anti-adenoviral efficacy of topical OKG-0301 in the Ad5/NZW rabbit ocular model.
39 NZW rabbits were inoculated in both eyes with 1.5 x 106 PFU/eye of Ad5 after corneal scarification. On day 1, the rabbits were divided into 4 topical treatment groups: 1) 25 μM OKG-0301 (n=9); 2) 2.5 µM OKG-0301 (n=10); 3) Saline (Negative Control) (CON) (n=10); 4) 0.5% Cidofovir (Positive Antiviral Control) (CDV) (n=10). Rabbits were treated topically in both eyes 8x/day for 9 days except for CDV (2X/day for 7 days). All eyes were cultured for virus on Days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Viral titers and positive cultures were determined on A549 cells.
25 µM OKG-0301, 2.5 µM OKG-0301, and CDV reduced viral titers compared with CON on Days 3, 4, 5, 7, 11 (P≤0.05, Kruskal-Wallis). In addition, 25 µM OKG-0301 (Days 7, 9, 11), 2.5 µM OKG-0301 (Day 11), and CDV (Days 5, 7, 11) produced fewer Positive Cultures/Total on the days indicated compared with CON (P<0.02, Fisher Exact). Furthermore, 25 µM OKG-0301 (5.67 ± 0.97 days), 2.5 µM OKG-0301 (7.15 ± 2.11 days) and CDV (5.88 ± 1.36 days) reduced the Duration of Viral Shedding compared to CON (9.61 ± 2.87 days) (P<0.001, ANOVA) for all treatments. Comparing only the OKG-0301 groups, 25 µM OKG-0301 was significantly more effective than 2.5 µM OKG-0301 for reducing daily titers and Positive Cultures/Total on Day 7 and shortening the Duration of Viral Shedding (p≤0.05).
25 µM OKG-0301 and 2.5 µM OKG-0301 demonstrated significant antiviral efficacy compared with CON in the Ad5/NZW rabbit ocular model. The antiviral efficacy of the OKG-0301 groups was similar to that of the positive antiviral control, 0.5% CDV. OKG-0301 appears to be a promising candidate for a topical antiviral for adenoviral ocular infections and further development is indicated.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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