Antifungal drug ciclopirox olamine reduces HSV-1 replication and disease in mice

Area of Science:

• Virology
• Ophthalmology
• Pharmacology

Background:

• Herpes simplex virus (HSV)-1 and HSV-2 cause significant ocular infections, leading to potential blindness.
• Current treatments like acyclovir (ACV) have limitations, including incomplete viral suppression and the development of drug resistance.
• HSV replication relies on nucleotidyl transferase superfamily (NTS) enzymes, presenting a target for antiviral development.

Purpose of the Study:

• To evaluate the efficacy of ciclopirox olamine, an antifungal agent, as a repurposed topical treatment for HSV-1 ocular infections.
• To assess the impact of ciclopirox olamine on viral shedding, blepharitis, and acute/latent infection of the peripheral nervous system in a mouse model.

Main Methods:

• Topical administration of ciclopirox olamine to the eyes of HSV-1 infected mice.
• Comparison of treatment outcomes with saline control and acyclovir (ACV) treated groups.
• Assessment of viral shedding from the corneal epithelium, development of blepharitis, and HSV-1 infection in the peripheral nervous system.

Main Results:

• Topical ciclopirox olamine significantly reduced HSV-1 shedding from the corneal epithelium in a dose-dependent manner.
• Treatment with ciclopirox olamine decreased blepharitis development to levels comparable to ACV treatment.
• Ciclopirox olamine treatment also significantly reduced acute and latent HSV-1 infection in the peripheral nervous system.

Conclusions:

• Ciclopirox olamine demonstrates potent antiviral activity against HSV-1 in a preclinical ocular infection model.
• The findings support the repurposing of ciclopirox olamine as a topical agent for managing HSV infections.
• Further clinical development of ciclopirox olamine for HSV infections is warranted.