Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Viruses. 2021 Apr 11;13(4):659. doi: 10.3390/v13040659.
Dengue virus (DENV) is the causative pathogen in the life-threatening dengue hemorrhagic fever and dengue shock syndrome. DENV is transmitted to humans via the bite of an infected mosquito. Approximately 100 million people are infected annually worldwide, and most of those live in tropical and subtropical areas. There is still no effective drug or vaccine for treatment of DENV infection. In this study, we set forth to investigate the effect of melatonin, which is a natural hormone with multiple pharmacological functions, against DENV infection. Treatment with subtoxic doses of melatonin dose-dependently inhibited DENV production. Cross-protection across serotypes and various cell types was also observed. Time-of-addition assay suggested that melatonin exerts its influence during the post-entry step of viral infection. The antiviral activity of melatonin partly originates from activation of the sirtuin pathway since co-treatment with melatonin and the sirtuin 1 (SIRT1) inhibitor reversed the effect of melatonin treatment alone. Moreover, melatonin could modulate the transcription of antiviral genes that aid in suppression of DENV production. This antiviral mechanism of melatonin suggests a possible new strategy for treating DENV infection.
登革热病毒（DENV）是导致危及生命的登革出血热和登革休克综合征的病原体。DENV 通过受感染蚊子的叮咬传播给人类。全球每年约有 1 亿人感染，其中大多数生活在热带和亚热带地区。目前尚无针对 DENV 感染的有效药物或疫苗。在这项研究中，我们着手研究褪黑素（一种具有多种药理作用的天然激素）对 DENV 感染的影响。用亚毒性剂量的褪黑素处理可剂量依赖性地抑制 DENV 的产生。还观察到针对不同血清型和各种细胞类型的交叉保护作用。添加时间测定表明，褪黑素在病毒感染的进入后阶段发挥作用。褪黑素的抗病毒活性部分源自于沉默信息调节因子 1（SIRT1）途径的激活，因为褪黑素和 SIRT1 抑制剂的共同处理逆转了单独使用褪黑素处理的效果。此外，褪黑素可以调节抗病毒基因的转录，从而有助于抑制 DENV 的产生。褪黑素的这种抗病毒机制提示了一种治疗 DENV 感染的新策略。
