A proof-of-concept study for the efficacy of dispirotripiperazine PDSTP in a rabbit model of herpes simplex epithelial keratitis

Herpes simplex keratitis is an important infectious cause of blindness worldwide. The mainstay of antiviral therapy is treatment with long-established nucleoside analogues orally or topically. However, the emergence of resistant strains may become a major health concern in the future. Therefore, the development of backup antiherpetic medicines is urgently needed. Small molecule PDSTP is known to be active against herpes simplex type 1 strains in vitro, affecting early host-pathogen interactions. Here, we evaluated its preclinical efficacy in a rabbit model of herpes simplex epithelial keratitis. The mean course of keratitis and the corneal lesions in the 1.0% PDSTP gel group was statistically significantly less than in the negative control group and was comparable to that in the aciclovir group. These findings open up new opportunities for the development of antiherpetic drugs with an original mechanism of action.

Automated summary

Herpes simplex keratitis is a significant cause of blindness worldwide. The current antiviral treatment may face resistance issues, highlighting the urgent need for backup medications. The small molecule PDSTP has shown activity against herpes simplex type 1 strains in vitro and demonstrated preclinical efficacy in a rabbit model of herpes simplex epithelial keratitis. These findings provide new opportunities for the development of antiherpetic drugs with a novel mechanism of action.