PDF(Pubmed)
Abstract：
UNASSIGNED: Oral herpes infections caused by herpes simplex virus type 1 (HSV-1) are one of the most common in the human population. Recently, they have been classified as an increasing problem in immunocompromised patients and those suffering from chronic inflammation of the oral mucosa and gums. Treatment mainly involves nucleoside analogues, such as acyclovir and its derivatives, which reduce virus replication and shedding. As drug-resistant strains of herpes emerge rapidly, there is a need for the development of novel anti-herpes agents. The aim of the study was to design an antiviral peptide, based on natural compounds, non-toxic to the host, and efficient against drug-resistant HSV-1. Here, we designed a lysine-rich derivative of amphibian temporin-1CEb conjugated to peptides penetrating the host cell membrane and examined their activity against HSV-1 infection of oral mucosa.
UNASSIGNED: We assessed the antiviral efficiency of the tested compound in simple 2D cell models (VeroE6 and TIGKs cells) and a 3D organotypic model of human gingiva (OTG) using titration assay, qPCR, and confocal imaging. To identify the molecular mechanism of antiviral activity, we applied the Azure A metachromatic test, and attachment assays techniques. Toxicity of the conjugates was examined using XTT and LDH assays.
UNASSIGNED: Our results showed that temporin-1CEb analogues significantly reduce viral replication in oral mucosa. The mechanism of peptide analogues is based on the interaction with heparan sulfate, leading to the reduce attachment of HSV-1 to the cell membrane. Moreover, temporin-1CEb conjugates effectively penetrate the gingival tissue being effective against acyclovir-resistant strains. Collectively, we showed that temporin-1CEb can be regarded as a novel, naturally derived antiviral compound for HSV-1 treatment.
UNASSIGNED: We assessed the antiviral efficiency of the tested compound in simple 2D cell models (VeroE6 and TIGKs cells) and a 3D organotypic model of human gingiva (OTG) using titration assay, qPCR, and confocal imaging. To identify the molecular mechanism of antiviral activity, we applied the Azure A metachromatic test, and attachment assays techniques. Toxicity of the conjugates was examined using XTT and LDH assays.
UNASSIGNED: Our results showed that temporin-1CEb analogues significantly reduce viral replication in oral mucosa. The mechanism of peptide analogues is based on the interaction with heparan sulfate, leading to the reduce attachment of HSV-1 to the cell membrane. Moreover, temporin-1CEb conjugates effectively penetrate the gingival tissue being effective against acyclovir-resistant strains. Collectively, we showed that temporin-1CEb can be regarded as a novel, naturally derived antiviral compound for HSV-1 treatment.
摘要：
■由1型单纯疱疹病毒（HSV-1）引起的口腔疱疹感染是人群中最常见的感染之一。最近,在免疫功能低下的患者以及患有口腔粘膜和牙龈慢性炎症的患者中，它们已被列为日益严重的问题。治疗主要涉及核苷类似物，如阿昔洛韦及其衍生物，减少病毒复制和脱落。随着疱疹的耐药菌株迅速出现，需要开发新的抗疱疹药物。这项研究的目的是设计一种抗病毒肽，基于天然化合物，对宿主无毒，并有效对抗耐药HSV-1。这里,我们设计了一种富含赖氨酸的两栖动物temporin-1CEb衍生物，该衍生物与穿透宿主细胞膜的肽偶联，并检查了它们对口腔粘膜HSV-1感染的活性。
■我们在简单的2D细胞模型（VeroE6和TIGKs细胞）和人牙龈（OTG）的3D器官型模型中使用滴定测定评估了测试化合物的抗病毒效率，qPCR,和共聚焦成像。为了确定抗病毒活性的分子机制，我们应用了AzureA变色测试，和附件测定技术。使用XTT和LDH测定法检查缀合物的毒性。
■我们的结果表明，temporin-1CEb类似物可显着减少口腔粘膜中的病毒复制。肽类似物的机制是基于与硫酸乙酰肝素的相互作用，导致HSV-1对细胞膜的附着减少。此外，temporin-1CEb缀合物有效地穿透牙龈组织,对阿昔洛韦抗性菌株有效。总的来说，我们表明，temporin-1CEb可以被视为一部小说，用于HSV-1治疗的天然来源的抗病毒化合物。
■我们在简单的2D细胞模型（VeroE6和TIGKs细胞）和人牙龈（OTG）的3D器官型模型中使用滴定测定评估了测试化合物的抗病毒效率，qPCR,和共聚焦成像。为了确定抗病毒活性的分子机制，我们应用了AzureA变色测试，和附件测定技术。使用XTT和LDH测定法检查缀合物的毒性。
■我们的结果表明，temporin-1CEb类似物可显着减少口腔粘膜中的病毒复制。肽类似物的机制是基于与硫酸乙酰肝素的相互作用，导致HSV-1对细胞膜的附着减少。此外，temporin-1CEb缀合物有效地穿透牙龈组织,对阿昔洛韦抗性菌株有效。总的来说，我们表明，temporin-1CEb可以被视为一部小说，用于HSV-1治疗的天然来源的抗病毒化合物。
