Background
Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis which, though usually self-limiting, may persist or progress without treatment.

Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis

In the present study the antiviral properties of the bacteriocin subtilosin against Herpes simplex virus type 1 (HSV-1) and the safety and efficacy of a subtilosin-based nanofiber formulation were determined. High concentrations of subtilosin, the cyclical antimicrobial peptide produced by Bacillus amyloliquefaciens, were virucidal against HSV-1. Interestingly, at non-virucidal concentrations, subtilosin inhibited wild type HSV-1 and aciclovir-resistant mutants in a dose-dependent manner. Although the exact antiviral mechanism is not fully understood, time of addition experiments and western blot analysis suggest that subtilosin does not affect viral multiplication steps prior to protein synthesis. Poly(vinyl alcohol) (PVOH)-based subtilosin nanofibers with a width of 278 nm were produced by the electrospinning process. The retained antimicrobial activity of the subtilosin-based fibers was determined via an agar well diffusion assay. The loading capacity of the fibers was 2.4 mg subtilosin/g fiber, and loading efficiency was 31.6%. Furthermore, the nanofibers with and without incorporated subtilosin were shown to be nontoxic to human epidermal tissues using an in vitro human tissue model. Taking together these results subtilosin-based nanofibers should be further studied as a novel alternative method for treatment and/or control of HSV-1 infection.

https://link.springer.com/content/pdf/10.1007%2Fs12602-013-9128-0.pdf

Safety, formulation, and in vitro antiviral activity of the antimicrobial peptide subtilosin against herpes simplex virus type 1.

Comparison of the Efficacy of Valacyclovir vs Acyclovir for the Prevention of Recurrent Herpes Simplex Virus Eye Disease

We investigated thymidine kinase (tk) mutants isolated during multiple episodes of recurrent bilateral acyclovir resistant herpes simplex keratitis in an immunocompetent patient. From one eye, we found a single guanine insertion, previously shown to greatly reduce TK expression, and from the other, a previously unidentified substitution, which genetic experiments confirmed confers drug resistance. The substitution, although distant from substrate binding sites, reduced thymidine phosphorylation 10-20-fold, and acyclovir phosphorylation >100-fold. This phenotype should permit reactivation from latency to cause recurrent disease. The results may have implications for the prevalence and prevention of acyclovir resistance in patients with herpes simplex keratitis.

/pdf/common-and-new-acyclovir-resistant-herpes-simplex-virus-1-71g01ihk62.pdf

Common and New Acyclovir Resistant Herpes Simplex Virus-1 Mutants Causing Bilateral Recurrent Herpetic Keratitis in an Immunocompetent Patient

Purpose
Biotinylated lipid prodrugs of acyclovir (ACV) were designed to target the sodium dependent multivitamin transporter (SMVT) on the cornea to facilitate enhanced cellular absorption of ACV.

Novel biotinylated lipid prodrugs of acyclovir for the treatment of herpetic keratitis (HK): transporter recognition, tissue stability and antiviral activity.

Herpes simplex virus (HSV) keratitis is a common cause of ocular morbidity. Resistance to aciclovir is probably under recognized. We describe three cases of aciclovir-resistant herpes simplex virus keratitis treated with systemic foscarnet and present a review of the pharmacological options available to manage this condition.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1442-9071.2010.02209.x

Aciclovir-resistant herpes keratitis.

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Aciclovir-resistant herpes keratitis.