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Filociclovir Is an Active Antiviral Agent against Ocular Adenovirus Isolates In Vitro and in the Ad5/NZW Rabbit Ocular Model.

Authors :
Romanowski EG
Hussein ITM
Cardinale SC
Butler MM
Morin LR
Bowlin TL
Yates KA
Shanks RMQ
Kowalski RP
Source :
Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2021 Mar 26; Vol. 14 (4). Date of Electronic Publication: 2021 Mar 26.
Publication Year :
2021

Abstract

Presently, there is no FDA- or EMA-approved antiviral for the treatment of human adenovirus (HAdV) ocular infections. This study determined the antiviral activity of filociclovir (FCV) against ocular HAdV isolates in vitro and in the Ad5/NZW rabbit ocular model. The 50% effective concentrations (EC <subscript>50</subscript> ) of FCV and cidofovir (CDV) were determined for several ocular HAdV types using standard plaque reduction assays. Rabbits were topically inoculated in both eyes with HAdV5. On day 1, the rabbits were divided into four topical treatment groups: (1) 0.5% FCV 4x/day × 10 d; (2) 0.1% FCV 4x/day × 10 d; (3) 0.5% CDV 2x/day × 7 d; (4) vehicle 4x/day × 10 d. Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. The resulting viral eye titers were determined using standard plaque assays. The mean in vitro EC <subscript>50</subscript> for FCV against tested HAdV types ranged from 0.50 to 4.68 µM, whereas those treated with CDV ranged from 0.49 to 30.3 µM. In vivo, compared to vehicle, 0.5% FCV, 0.1% FCV, and 0.5% CDV produced lower eye titers, fewer numbers of positive eye cultures, and shorter durations of eye infection. FCV demonstrated anti-adenovirus activity in vitro and in vivo.

Details

Language :
English
ISSN :
1424-8247
Volume :
14
Issue :
4
Database :
MEDLINE
Journal :
Pharmaceuticals (Basel, Switzerland)
Publication Type :
Academic Journal
Accession number :
33810229
Full Text :
https://doi.org/10.3390/ph14040294