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二螺哌嗪PDSTP在单纯疱疹性上皮性角膜炎兔模型中的疗效的概念验证研究。

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

作者信息

Alimbarova Lyudmila, Egorova Anna, Riabova Olga, Monakhova Natalia, Makarov Vadim

机构信息

Gamaleya National Research Centre of Epidemiology and Microbiology of the Ministry of Health of Russia, 18 Gamaleya Street, 123098, Moscow, Russia.

Research Centre of Biotechnology RAS, 33-2 Leninsky Prospect, 119071, Moscow, Russia.

出版信息

Antiviral Res. 2022 Jun;202:105327. doi: 10.1016/j.antiviral.2022.105327. Epub 2022 Apr 27.

Abstract

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.

摘要

单纯疱疹性角膜炎是全球范围内导致失明的重要感染性病因。抗病毒治疗的主要手段是使用长期以来一直使用的核苷类似物进行口服或局部治疗。然而,耐药菌株的出现可能在未来成为一个主要的健康问题。因此,迫切需要开发备用的抗疱疹药物。已知小分子PDSTP在体外对1型单纯疱疹病毒株具有活性,可影响早期宿主与病原体的相互作用。在此,我们在单纯疱疹性上皮性角膜炎的兔模型中评估了其临床前疗效。1.0% PDSTP凝胶组的角膜炎平均病程和角膜病变在统计学上显著少于阴性对照组,且与阿昔洛韦组相当。这些发现为开发具有原始作用机制的抗疱疹药物开辟了新的机会。

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