{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:18:39Z","timestamp":1760149119651,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"NIH","doi-asserted-by":"publisher","award":["EY08227","EY08098"],"award-info":[{"award-number":["EY08227","EY08098"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH Core Grant for Vision Research","award":["EY08227","EY08098"],"award-info":[{"award-number":["EY08227","EY08098"]}]},{"name":"Eye &amp; Ear Foundation of Pittsburgh","award":["EY08227","EY08098"],"award-info":[{"award-number":["EY08227","EY08098"]}]},{"name":"University of Pittsburgh Department of Ophthalmology","award":["EY08227","EY08098"],"award-info":[{"award-number":["EY08227","EY08098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Adenoviruses are the major cause of ocular viral infections worldwide. Currently, there is no approved antiviral treatment for these eye infections. Cyclopentenylcytosine (CPE-C) is an antiviral that has demonstrated activity against more than 20 viruses. The goals of the current study were to determine the in vitro and in vivo antiviral activity of CPE-C as well as its ocular toxicity. Antiviral activity was evaluated in vitro using standard plaque reduction assays to determine the 50% effective concentrations (EC50s) and in vivo in the Ad5\/NZW rabbit ocular replication model. Ocular toxicity was determined in uninfected rabbit eyes following topical ocular application. The in vitro EC50s for CPE-C ranged from 0.03 to 0.059 \u03bcg\/mL for nine adenovirus types that commonly infect the eye. Ocular toxicity testing determined CPE-C to be non-irritating or practically non-irritating by Draize scoring. In vivo, 3% CPE-C topically administered 4X or 2X daily for 7 days to adenovirus-infected eyes demonstrated effective antiviral activity compared with the negative control and comparable antiviral activity to the positive control, 0.5% cidofovir, topically administered twice daily for 7 days. We conclude CPE-C was relatively non-toxic to rabbit eyes and demonstrated potent anti-adenoviral activity in vitro and in vivo.<\/jats:p>","DOI":"10.3390\/molecules28135078","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T01:43:13Z","timestamp":1688002993000},"page":"5078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cyclopentenylcytosine (CPE-C): In Vitro and In Vivo Evaluation as an Antiviral against Adenoviral Ocular Infections"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4246-3276","authenticated-orcid":false,"given":"Eric G.","family":"Romanowski","sequence":"first","affiliation":[{"name":"The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Vision Institute, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8995-8121","authenticated-orcid":false,"given":"Kathleen A.","family":"Yates","sequence":"additional","affiliation":[{"name":"The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Vision Institute, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y. Jerold","family":"Gordon","sequence":"additional","affiliation":[{"name":"The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Vision Institute, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"unstructured":"Pepose, J.S., Holland, G.N., and Wilhelmus, K.R. (1996). Ocular Infection & Immunity, Mosby.","key":"ref_1"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/ICO.0b013e31816060bb","article-title":"The possibility of human adenovirus detection from the conjunctiva in asymptomatic cases during nosocomial infection","volume":"27","author":"Kaneko","year":"2008","journal-title":"Cornea"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/rmv.589","article-title":"Clinical features and treatment of adenovirus infections","volume":"18","author":"Lenaerts","year":"2008","journal-title":"Rev. Med. 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