PDF(Pubmed)
Abstract：
Herpes simplex virus (HSV) infections are highly widespread among humans, producing symptoms ranging from ulcerative lesions to severe diseases such as blindness and life-threatening encephalitis. At present, there are no vaccines available, and some existing antiviral treatments can be ineffective or lead to adverse effects. As a result, there is a need for new anti-HSV drugs. In this report, the in vitro anti-HSV effect of 9,9\'-norharmane dimer (nHo-dimer), which belongs to the β-carboline (βC) alkaloid family, was evaluated. The dimer exhibited no virucidal properties and did not impede either the attachment or penetration steps of viral particles. The antiviral effect was only exerted under the constant presence of the dimer in the incubation media, and the mechanism of action was found to involve later events of virus infection. Analysis of fluorescence lifetime imaging data showed that the nHo-dimer internalized well into the cells when present in the extracellular incubation medium, with a preferential accumulation into perinuclear organelles including mitochondria. After washing the host cells with fresh medium free of nHo-dimer, the signal decreased, suggesting the partial release of the compound from the cells. This agrees with the observation that the antiviral effect is solely manifested when the alkaloid is consistently present in the incubation media.
摘要：
单纯疱疹病毒（HSV）感染在人类中非常普遍，产生从溃疡性病变到失明和危及生命的脑炎等严重疾病的症状。目前,没有可用的疫苗，和一些现有的抗病毒治疗可能是无效的或导致不良反应。因此,需要新的抗HSV药物。在这份报告中,9,9'-norharmane二聚体（nHo-二聚体）的体外抗HSV作用，属于β-咔啉（βC）生物碱家族，进行了评估。二聚体没有表现出杀病毒性质,并且不妨碍病毒颗粒的附着或渗透步骤。只有在孵育培养基中二聚体的恒定存在下才能发挥抗病毒作用。并且发现其作用机制涉及后来的病毒感染事件。荧光寿命成像数据的分析表明，当存在于细胞外孵育培养基中时，nHo-二聚体很好地内化到细胞中，优先积累到包括线粒体在内的核周细胞器中。用不含nHo-二聚体的新鲜培养基洗涤宿主细胞后，信号减弱,表明化合物从细胞中部分释放。这与以下观察结果一致：当生物碱始终存在于孵育培养基中时，抗病毒作用仅表现出来。
