As one of the highly contagious forms, herpes simplex virus type 2 (HSV-2) commonly caused severe genital diseases and closely referred to the HIV infection. The lack of effective vaccines and drug-resistance proclaimed the preoccupation for alternative antiviral agents against HSV-2. Molecules bearing indole nucleus presented diverse biological properties involving antiviral and anti-inflammatory activities. In this study, one of the indole molecules, arbidol derivative (ARD) was designed and synthesized prior to the evaluation of its anti-HSV-2 activity. Our data showed that the ARD effectively suppressed HSV-2-induced cytopathic effects and the generation of progeny virus, with 50% effective concentrations of 3.386 and 1.717 μg/mL, respectively. The results of the time-course assay suggested that the ARD operated in a dual antiviral way by interfering virus entry and impairing the earlier period of viral cycle during viral DNA synthesis. The ARD-mediated HSV-2 inhibition was partially attained by blocking NF-B pathways and down-regulating the expressions of several inflammatory cytokines. Furthermore, studies showed that oral administration of ARD protected BALB/c mice from intravaginal HSV-2 challenge by alleviating serious vulval lesions and histopathological changes in the target organs. Besides, the treatment with ARD also made the levels of viral protein, NF-B protein and inflammatory cytokines lower, in consistent with the studies. Collectively, ARD unveiled therapeutic potential for the prevention and treatment of HSV-2 infections.

中文翻译：

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在人宫颈上皮细胞和 BALB/c 小鼠中评估新型阿比朵尔衍生物对单纯疱疹病毒 II 的作用


作为一种高度传染性的病毒，2 型单纯疱疹病毒 (HSV-2) 通常会引起严重的生殖器疾病，与 HIV 感染密切相关。由于缺乏有效的疫苗和耐药性，人们开始关注针对 HSV-2 的替代抗病毒药物。带有吲哚核的分子具有多种生物学特性，包括抗病毒和抗炎活性。在这项研究中，设计并合成了一种吲哚分子阿比朵尔衍生物（ARD），然后评估其抗 HSV-2 活性。我们的数据显示，ARD 有效抑制 HSV-2 诱导的细胞病变效应和子代病毒的产生，50% 有效浓度分别为 3.386 和 1.717 μg/mL。时程测定的结果表明，ARD 通过干扰病毒进入并损害病毒 DNA 合成过程中的病毒周期早期，以双重抗病毒方式发挥作用。 ARD 介导的 HSV-2 抑制部分是通过阻断 NF-B 通路和下调几种炎症细胞因子的表达来实现的。此外，研究表明，口服 ARD 可减轻严重的外阴病变和靶器官的组织病理学变化，从而保护 BALB/c 小鼠免受阴道内 HSV-2 的攻击。此外，ARD治疗还降低了病毒蛋白、NF-B蛋白和炎症细胞因子的水平，这与研究结果一致。总的来说，ARD 揭示了预防和治疗 HSV-2 感染的治疗潜力。