In vitro cytotoxicity and antiviral efficacy against feline herpesvirus type 1 of famciclovir and its metabolites

Allyson D. Groth, Marcos T. Contreras, Helen K. Kado-Fong, Kyvan Q. Nguyen, Sara M Thomasy, David J Maggs

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: To assess in vitro the antiviral efficacy against feline herpesvirus (FHV-1) and cytotoxicity for cultured feline cells of famciclovir and its metabolites, BRL 42359 and penciclovir. To investigate the effect of timing of penciclovir application on in vitro antiviral activity. Procedures: Plaque reduction assays were used to estimate antiviral efficacy of all compounds and the effect of penciclovir exposure before or after exposure to a FHV-1 field isolate. Cytotoxicity was evaluated by assessing cell morphology and viable cell number for 72 h following exposure to each compound. Results: The penciclovir concentration that inhibited FHV-1-induced plaque formation by 50% (IC50) was 0.86 μg/mL (3.4 μm). Famciclovir and BRL 42359 had no antiviral effect against FHV-1 at any concentration assessed. Antiviral activity was significantly enhanced when cells were exposed to 4 μm penciclovir (approximate IC50) for 1 h but not for 24 h before viral adsorption. Delaying exposure of cells to penciclovir for 1, 2, or 4 h after viral adsorption significantly enhanced antiviral activity. Relative to untreated control wells, >88% of cells remained viable when exposed to famciclovir (100 μm), BRL 42359 (1.06 mm), or penciclovir (40 μm) for 72 h. No morphologic evidence of cytotoxicity was noted. Conclusions: Penciclovir demonstrates potent antiviral activity against FHV-1 and may be effective at lower tissue, tear, and plasma concentrations than previously targeted. The duration of in vitro antiviral effect of penciclovir suggests that frequent famciclovir administration may be necessary in vivo. Famciclovir and BRL 42359 showed no signs of in vitro cytotoxicity.

Original languageEnglish (US)
Pages (from-to)268-274
Number of pages7
JournalVeterinary Ophthalmology
Volume17
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Felid herpesvirus 1
Herpesviridae
Felidae
Antiviral Agents
cytotoxicity
metabolites
cells
inhibitory concentration 50
adsorption
Inhibitory Concentration 50
Adsorption
application timing
famciclovir
penciclovir
In Vitro Techniques
cats
Tears
duration
Cultured Cells
assays

Keywords

  • Antiviral drugs
  • Cat
  • Herpetic disease
  • Penciclovir
  • Virology

ASJC Scopus subject areas

  • veterinary(all)
  • Medicine(all)

Cite this

In vitro cytotoxicity and antiviral efficacy against feline herpesvirus type 1 of famciclovir and its metabolites. / Groth, Allyson D.; Contreras, Marcos T.; Kado-Fong, Helen K.; Nguyen, Kyvan Q.; Thomasy, Sara M; Maggs, David J.

In: Veterinary Ophthalmology, Vol. 17, No. 4, 2014, p. 268-274.

Research output: Contribution to journalArticle

Groth, Allyson D. ; Contreras, Marcos T. ; Kado-Fong, Helen K. ; Nguyen, Kyvan Q. ; Thomasy, Sara M ; Maggs, David J. / In vitro cytotoxicity and antiviral efficacy against feline herpesvirus type 1 of famciclovir and its metabolites. In: Veterinary Ophthalmology. 2014 ; Vol. 17, No. 4. pp. 268-274.
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abstract = "Objectives: To assess in vitro the antiviral efficacy against feline herpesvirus (FHV-1) and cytotoxicity for cultured feline cells of famciclovir and its metabolites, BRL 42359 and penciclovir. To investigate the effect of timing of penciclovir application on in vitro antiviral activity. Procedures: Plaque reduction assays were used to estimate antiviral efficacy of all compounds and the effect of penciclovir exposure before or after exposure to a FHV-1 field isolate. Cytotoxicity was evaluated by assessing cell morphology and viable cell number for 72 h following exposure to each compound. Results: The penciclovir concentration that inhibited FHV-1-induced plaque formation by 50{\%} (IC50) was 0.86 μg/mL (3.4 μm). Famciclovir and BRL 42359 had no antiviral effect against FHV-1 at any concentration assessed. Antiviral activity was significantly enhanced when cells were exposed to 4 μm penciclovir (approximate IC50) for 1 h but not for 24 h before viral adsorption. Delaying exposure of cells to penciclovir for 1, 2, or 4 h after viral adsorption significantly enhanced antiviral activity. Relative to untreated control wells, >88{\%} of cells remained viable when exposed to famciclovir (100 μm), BRL 42359 (1.06 mm), or penciclovir (40 μm) for 72 h. No morphologic evidence of cytotoxicity was noted. Conclusions: Penciclovir demonstrates potent antiviral activity against FHV-1 and may be effective at lower tissue, tear, and plasma concentrations than previously targeted. The duration of in vitro antiviral effect of penciclovir suggests that frequent famciclovir administration may be necessary in vivo. Famciclovir and BRL 42359 showed no signs of in vitro cytotoxicity.",
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T1 - In vitro cytotoxicity and antiviral efficacy against feline herpesvirus type 1 of famciclovir and its metabolites

AU - Groth, Allyson D.

AU - Contreras, Marcos T.

AU - Kado-Fong, Helen K.

AU - Nguyen, Kyvan Q.

AU - Thomasy, Sara M

AU - Maggs, David J

PY - 2014

Y1 - 2014

N2 - Objectives: To assess in vitro the antiviral efficacy against feline herpesvirus (FHV-1) and cytotoxicity for cultured feline cells of famciclovir and its metabolites, BRL 42359 and penciclovir. To investigate the effect of timing of penciclovir application on in vitro antiviral activity. Procedures: Plaque reduction assays were used to estimate antiviral efficacy of all compounds and the effect of penciclovir exposure before or after exposure to a FHV-1 field isolate. Cytotoxicity was evaluated by assessing cell morphology and viable cell number for 72 h following exposure to each compound. Results: The penciclovir concentration that inhibited FHV-1-induced plaque formation by 50% (IC50) was 0.86 μg/mL (3.4 μm). Famciclovir and BRL 42359 had no antiviral effect against FHV-1 at any concentration assessed. Antiviral activity was significantly enhanced when cells were exposed to 4 μm penciclovir (approximate IC50) for 1 h but not for 24 h before viral adsorption. Delaying exposure of cells to penciclovir for 1, 2, or 4 h after viral adsorption significantly enhanced antiviral activity. Relative to untreated control wells, >88% of cells remained viable when exposed to famciclovir (100 μm), BRL 42359 (1.06 mm), or penciclovir (40 μm) for 72 h. No morphologic evidence of cytotoxicity was noted. Conclusions: Penciclovir demonstrates potent antiviral activity against FHV-1 and may be effective at lower tissue, tear, and plasma concentrations than previously targeted. The duration of in vitro antiviral effect of penciclovir suggests that frequent famciclovir administration may be necessary in vivo. Famciclovir and BRL 42359 showed no signs of in vitro cytotoxicity.

AB - Objectives: To assess in vitro the antiviral efficacy against feline herpesvirus (FHV-1) and cytotoxicity for cultured feline cells of famciclovir and its metabolites, BRL 42359 and penciclovir. To investigate the effect of timing of penciclovir application on in vitro antiviral activity. Procedures: Plaque reduction assays were used to estimate antiviral efficacy of all compounds and the effect of penciclovir exposure before or after exposure to a FHV-1 field isolate. Cytotoxicity was evaluated by assessing cell morphology and viable cell number for 72 h following exposure to each compound. Results: The penciclovir concentration that inhibited FHV-1-induced plaque formation by 50% (IC50) was 0.86 μg/mL (3.4 μm). Famciclovir and BRL 42359 had no antiviral effect against FHV-1 at any concentration assessed. Antiviral activity was significantly enhanced when cells were exposed to 4 μm penciclovir (approximate IC50) for 1 h but not for 24 h before viral adsorption. Delaying exposure of cells to penciclovir for 1, 2, or 4 h after viral adsorption significantly enhanced antiviral activity. Relative to untreated control wells, >88% of cells remained viable when exposed to famciclovir (100 μm), BRL 42359 (1.06 mm), or penciclovir (40 μm) for 72 h. No morphologic evidence of cytotoxicity was noted. Conclusions: Penciclovir demonstrates potent antiviral activity against FHV-1 and may be effective at lower tissue, tear, and plasma concentrations than previously targeted. The duration of in vitro antiviral effect of penciclovir suggests that frequent famciclovir administration may be necessary in vivo. Famciclovir and BRL 42359 showed no signs of in vitro cytotoxicity.

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KW - Cat

KW - Herpetic disease

KW - Penciclovir

KW - Virology

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