Pilot Study of the Safety and Tolerability of a Subconjunctival Penciclovir Implant in Cats Experimentally Infected with Herpesvirus

Covert, Jill; Thomasy, Sara M; Kado-Fong, Helen; Kon, Leslie N.; Kass, Philip H.; Reilly, Christopher M.; Lappin, Michael R.; Margulies, Barry J.; Maggs, David J.

doi:10.1089/jop.2018.0043

Cited by 4 publications

(2 citation statements)

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“…This drug belongs to a family of nucleoside analogue agents that inhibit viral replication by truncating nucleotide strands during viral DNA production. They are the primary means of treating herpes simplex keratitis in human patients [ 37 ] and have been studied extensively in vitro and in vivo for use against other herpesviruses causing ophthalmic disease in domestic animal species, particularly cats [ 10 , 11 , 12 , 14 , 15 , 18 , 19 , 38 , 39 , 40 , 41 ]. Cidofovir inhibition of BoHV-1 has been studied previously, with Gilliam and Field calculating an in-vitro IC 50Number of 10 μg/mL (35.8 μM) [ 23 ], which is very similar to our independently calculated value described here (39.7 μM).…”

Section: Discussionmentioning

confidence: 99%

“…Of course, the logistical difficulties of topical ophthalmic treatment in cattle merit further investigation into alternate modes of drug delivery. For example, a subconjunctival penciclovir implant was recently developed for the treatment of herpetic keratoconjunctivitis in cats [ 40 ], which may also prove to be a useful strategy for extended drug release in cattle that can only be handled infrequently.…”

Section: Discussionmentioning

confidence: 99%

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Assessment of Cidofovir for Treatment of Ocular Bovine Herpesvirus-1 Infection in Cattle Using an Ex-Vivo Model

Alling

Liu

Langohr

et al. 2021

Viruses

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Bovine herpesvirus-1 (BoHV-1) infection contributes to keratoconjunctivitis, respiratory disease, and reproductive losses in cattle. The objective of this study was to determine the most appropriate ophthalmic antiviral agent for BoHV-1 inhibition using in-vitro culture and novel ex-vivo bovine corneal modeling. Half-maximal inhibitory concentrations of BoHV-1 were determined for cidofovir, ganciclovir, idoxuridine, and trifluridine via in-vitro plaque reduction assays. In-vitro cytotoxicity was compared amongst these compounds via luciferase assays. Trifluridine and cidofovir were the most potent BoHV-1 inhibitors in vitro, while trifluridine and idoxuridine were the most cytotoxic agents. Therefore, cidofovir was the most potent non-cytotoxic agent and was employed in the ex-vivo corneal assay. Corneoscleral rings (n = 36) from fresh cadaver bovine globes were harvested and equally divided into an uninfected, untreated control group; a BoHV-1-infected, untreated group; and a BoHV-1-infected, cidofovir-treated group. Virus isolation for BoHV-1 titers was performed from corneal tissue and liquid media. Histologic measurements of corneal thickness, epithelial cell density, and tissue organization were compared between groups. Substantial BoHV-1 replication was observed in infected, untreated corneas, but BoHV-1 titer was significantly reduced in cidofovir-treated (1.69 ± 0.08 × 103 PFU/mL) versus untreated (8.25 ± 0.25 × 105 PFU/mL, p < 0.0001) tissues by day 2 of culture. No significant differences in histologic criteria were observed between groups. In conclusion, cidofovir warrants further investigation as treatment for BoHV-1 keratoconjunctivitis, with future studies needed to assess in-vivo tolerability and efficacy.

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