title: Pretreatment with topical 0.1% (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine inhibits adenovirus type 5 replication in the New Zealand rabbit ocular model.
abstract: Currently there is no clinically effective antiviral agent for the prevention or treatment of ocular adenoviral infections. Using a paired-eye, masked design, we tested the antiviral efficacy of topical 0.1% (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine in the New Zealand rabbit ocular model after topical and intrastromal inoculation with 100 microliters (4 x 10(5) plaque-forming units per eye) of adenovirus type 5 McEwen, a clinical isolate. Prevention studies involved pretreatment (six times a day) 1 day before inoculation and continuing for 4 additional days. Compared with the control eyes, the pretreated eyes showed a significant reduction in the peak viral eye titers on days 3, 4, 5, and 7 after treatment (p < 0.03-0.005), and a reduction in the duration of viral sheeding (p < 0.02). Rebound increase in adenoviral titers was detected in five of 20 eyes (25%) after cessation of treatment, suggesting a therapeutic effect and a need for further studies to optimize the treatment regimen.
authors.affiliation: Eye and Ear Institute of Pittsburgh, PA 15213.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Gordon
authors.forename: E
authors.initials: E
authors.lastname: Romanowski
authors.forename: T
authors.initials: T
authors.lastname: Araullo-Cruz
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000256:Adenoviridae / Q000502:physiology; D000257:Adenoviridae Infections / Q000382:microbiology / Q000517:prevention & control*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D000077404:Cidofovir; D015169:Colony Count, Microbial; D003316:Corneal Diseases / Q000382:microbiology / Q000517:prevention & control*; D003319:Corneal Stroma / Q000382:microbiology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D015828:Eye Infections, Viral / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D011292:Premedication; D011817:Rabbits; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir