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. 2023 Jun 29;28(13):5078.
doi: 10.3390/molecules28135078.

Cyclopentenylcytosine (CPE-C): In Vitro and In Vivo Evaluation as an Antiviral against Adenoviral Ocular Infections

Eric G Romanowski  1 , Kathleen A Yates  1 , Y Jerold Gordon  1
Affiliations

Cyclopentenylcytosine (CPE-C): In Vitro and In Vivo Evaluation as an Antiviral against Adenoviral Ocular Infections

Eric G Romanowski et al. Molecules. .

Abstract

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 μg/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.

Keywords: adenovirus; animal model; antiviral; conjunctivitis; cyclopentenylcytosine; eye; in vitro.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
This figure presents the chemical structures of (A) CPE-C and (B) cidofovir. Both are nucleoside analogs of cytosine.
Figure 2
Figure 2
This figure presents the percentages of daily HAdV5-positive cultures per Total for each group. 3% CPE-C 4X/day, 3% CPE-C 2X/day, and 0.5% cidofovir 2X/day significantly reduced the number of HAdV5-positive cultures per group on days 1, 3, 4, 5, 7, and 14 (p ≤ 0.0471, FET) compare with the saline control. There were no significant differences among the antiviral treatments on any of the culture days. In addition, 0.5% cidofovir 2X/day had significantly fewer HAdV5-positive cultures on day 9 than the saline control (p = 0.0197, FET).
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