Aliabadi Nasrin, Jamalidoust Marzieh, Pouladfar Gholamreza, Azarpira Negar, Ziyaeyan Atoosa, Ziyaeyan Mazyar
Department of Clinical Virology, Professor Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Heliyon. 2022 Aug 19;8(8):e10348. doi: 10.1016/j.heliyon.2022.e10348. eCollection 2022 Aug.
The emergence of Acyclovir-Resistant Herpes Simplex Virus type-1, which is the result of clinical over usage calls for the urgent need of a novel anti-HSV agent. Hence, the activity of Triptolide (TP) and (S)-10-Hydroxycamptothecin (10-HCPT) were investigated as natural products in two infection models of HSV-1.
The antiviral efficacy of TP and 10-HCPT was evaluated in mice ocular and cutaneous infection models of HSV. Groups of 10 mice were infected with HSV-1. Both compounds were administered topically on corneal and skin. The disease severity, viral titer (plaque reduction assay), and histopathology were evaluated in the ocular and cutaneous models of HSV-1 infection on days 3, 5, 7, 9, and 12 post infection, as well as genome loads on days 3 and 12.
Topical treatment of corneal with TP, 10-HCPT, and ACV was effective in reducing stromal disease (after day 3, 0.001), plus TP and ACV on vascularization (after day 7, = 0.001). The virus titer decreased significantly in the infected treated groups after day 3 (P < 0.05). Also, on day 12 post-infection, the virus genome volume in the TP and ACV groups was significantly reduced. With respect to virus titers and the DNA yield, significant difference was observed, merely in the ACV group in comparison to the control ( = 0.013). Immunohistochemistry analysis showed that corneal epithelium healing was partially visible in the 10-HCPT group, which gradually increased in TP, and was the highest in the ACV group. The skin epithelium healing was only observed in TP and ACV groups, and was superior in the ACV group.
This study revealed the virologic and clinical potential of TP to treat ocular mouse model.
由于临床过度使用导致的耐阿昔洛韦单纯疱疹病毒1型的出现，迫切需要一种新型抗单纯疱疹病毒药物。因此，研究了雷公藤甲素（TP）和（S）-10-羟基喜树碱（10-HCPT）作为天然产物在两种单纯疱疹病毒1型感染模型中的活性。
在单纯疱疹病毒的小鼠眼部和皮肤感染模型中评估TP和10-HCPT的抗病毒疗效。将10只小鼠分为一组，感染单纯疱疹病毒1型。两种化合物均局部应用于角膜和皮肤。在感染后第3、5、7、9和12天，对单纯疱疹病毒1型感染的眼部和皮肤模型的疾病严重程度、病毒滴度（蚀斑减少试验）和组织病理学进行评估，并在第3天和第12天评估基因组负荷。
用TP、10-HCPT和阿昔洛韦局部治疗角膜可有效减轻基质疾病（第3天后，P<0.001），TP和阿昔洛韦还可减轻血管化（第7天后，P<0.001）。感染治疗组在第3天后病毒滴度显著降低（P<0.05）。此外，在感染后第12天，TP组和阿昔洛韦组的病毒基因组体积显著减少。就病毒滴度和DNA产量而言，与对照组相比，仅阿昔洛韦组存在显著差异（P=0.013）。免疫组织化学分析表明，10-HCPT组角膜上皮愈合部分可见，在TP组中逐渐增加，在阿昔洛韦组中最高。仅在TP组和阿昔洛韦组观察到皮肤上皮愈合，且在阿昔洛韦组中更优。
本研究揭示了TP治疗小鼠眼部模型的病毒学和临床潜力。
