Prior inhibition of AKT phosphorylation by BX795 can define a safer strategy to prevent herpes simplex virus-1 infection of the eye.
BX795
Corneal toxicity
Herpes simplex virus
Prophylaxis
Topical
Journal
The ocular surface
ISSN: 1937-5913
Titre abrégé: Ocul Surf
Pays: United States
ID NLM: 101156063
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
29
10
2019
revised:
15
11
2019
accepted:
22
11
2019
pubmed:
27
11
2019
medline:
14
5
2021
entrez:
27
11
2019
Statut:
ppublish
Résumé
To evaluate the prophylactic antiviral efficacy, corneal tolerance and toxicity of topically dosed BX795, a non-nucleoside small-molecule inhibitor of herpes simplex virus type-1 (HSV-1). Prophylactic treatment with BX795 was performed both in-vitro on human corneal epithelial cells and in-vivo on mice prior to HSV-1 challenge. Viral burden was evaluated using a standard plaque assay. In a separate experiment, mice were treated topically 3-times daily for 4-weeks with BX795 to evaluate corneal tolerance and toxicity. Phenol-red thread measurements, fluorescein staining and optical coherence tomography (OCT) were used to evaluate tear production, dryness and corneal structural changes. Corneal sensitivity and intraocular pressure were measured using esthesiometery and tonometery respectively. Both in-vitro and in-vivo results showed a robust suppression of HSV-1 infection when treated prophylactically with BX795. The fluorescein stain and phenol-red results for the BX795-treated eyes did not show signs of corneal surface dryness when compared to trifluridine (TFT), an FDA-approved topical antiviral. The OCT measurements showed no signs of structural changes to the cornea suggesting that BX795 treatment was well tolerated without any apparent signs of toxicity or inflammation. The corneal sensitivity of BX795-treated eyes was not significantly different from TFT-treated eyes. No significant increase in the intraocular pressure of BX795-treated mice was observed. Prophylactic treatment with BX795 protects corneal cells from HSV-1 infection. The antiviral is well-tolerated on murine corneas without any detectable toxicity.
Identifiants
pubmed: 31770600
pii: S1542-0124(19)30421-5
doi: 10.1016/j.jtos.2019.11.011
pmc: PMC7268978
mid: NIHMS1586954
pii:
doi:
Substances chimiques
BX795
0
Pyrimidines
0
Thiophenes
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
221-230Subventions
Organisme : NEI NIH HHS
ID : P30 EY001792
Pays : United States
Organisme : BLRD VA
ID : I01 BX004080
Pays : United States
Organisme : NEI NIH HHS
ID : K08 EY024339
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY029409
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY024710
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
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