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Carnosine exhibits significant antiviral activity against Dengue and Zika virus.
Journal of Peptide Science ( IF 2.1 ) Pub Date : 2019-07-09 , DOI: 10.1002/psc.3196
Hussin A Rothan 1 , Ammar Yasir Abdulrahman 2 , Ahmad Suhail Khazali 2 , Nurshamimi Nor Rashid 2 , Teoh Teow Chong 3 , Rohana Yusof 2
Affiliation  

Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses transmitted to humans by their common vector, Aedes mosquitoes. DENV infection represents one of the most widely spread mosquito‐borne diseases whereas ZIKV infection occasionally re‐emerged in the past causing outbreaks. Although there have been considerable advances in understanding the pathophysiology of these viruses, no effective vaccines or antiviral drugs are currently available. In this study, we evaluated the antiviral activity of carnosine, an endogenous dipeptide (β‐alanyl‐l‐histidine), against DENV serotype 2 (DENV2) and ZIKV infection in human liver cells (Huh7). Computational studies were performed to predict the potential interactions between carnosine and viral proteins. Biochemical and cell‐based assays were performed to validate the computational results. Mode‐of‐inhibition, plaque reduction, and immunostaining assays were performed to determine the antiviral activity of carnosine. Exogenous carnosine showed minimal cytotoxicity in Huh7 cells and rescued the viability of infected cells with EC50 values of 52.3 and 59.5 μM for DENV2 and ZIKV infection, respectively. Based on the mode‐of‐inhibition assays, carnosine inhibited DENV2 mainly by inhibiting viral genome replication and interfering with virus entry. Carnosine antiviral activity was verified with immunostaining assay where carnosine treatment diminished viral fluorescence signal. In conclusion, carnosine exhibited significant inhibitory effects against DENV2 and ZIKV replication in human liver cells and could be utilized as a lead peptide for the development of effective and safe antiviral agents against DENV and ZIKV.

中文翻译:

肌肽对登革热和寨卡病毒表现出显着的抗病毒活性。

登革热病毒(DENV)和寨卡病毒(ZIKV)是通过共同的媒介伊蚊(Aedes mosquitoes )传播给人类的黄病毒。DENV感染是最广泛传播的蚊媒疾病之一,而ZIKV感染在过去偶尔会重新出现,从而引起暴发。尽管在了解这些病毒的病理生理学方面已有相当大的进步,但目前尚无有效的疫苗或抗病毒药物。在这项研究中,我们评估了肌肽的抗病毒活性,内源性肽(β丙氨-组氨酸),以抗人肝细胞中的DENV血清型2(DENV2)和ZIKV感染(Huh7)。进行了计算研究以预测肌肽和病毒蛋白之间的潜在相互作用。进行了生化和基于细胞的测定以验证计算结果。进行抑制模式,噬菌斑减少和免疫染色试验以确定肌肽的抗病毒活性。外源肌肽在Huh7细胞中显示出最小的细胞毒性,并挽救了EC 50感染细胞的生存能力DENV2和ZIKV感染的52.3μM和59.5μM值。根据抑制模式分析,肌肽主要通过抑制病毒基因组复制和干扰病毒进入来抑制DENV2。肌肽的抗病毒活性通过免疫染色法进行了验证,其中肌肽的处理减少了病毒荧光信号。总之,肌肽对人肝细胞中的DENV2和ZIKV复制表现出显着的抑制作用,可以用作开发DENV和ZIKV的安全有效抗病毒剂的先导肽。
更新日期:2019-07-09
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