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一种硫胺石抑制了登革热病毒,其潜在目标是在病毒甲基转移酶的SAM结合部位

Van Cao¹, I Putu Sukanadi², Naphat Loeanurit³

¹Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Interdisciplinary Program in Microbiology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand; DaNang University of Medical Technology and Pharmacy, DaNang, 50200, Viet Nam.

Antiviral research

|November 15, 2023

概括

新的硫胺石衍生物在抑制登革热病毒 (DENV) 方面表现有前途. 化合物SC27针对病毒甲基转移酶,为登革热感染提供了潜在的新治疗途径.

科学领域:

病毒学病毒学
药用化学医学化学
药物发现药物发现药物发现

背景情况:

登革热病毒 (DENV) 感染是一个日益严重的全球健康问题,气候变化加剧了这一问题,导致血泄漏和出血性休克等严重并发症.
目前的DENV治疗主要是辅助性,突显了迫切需要新型抗病毒疗法.
黄类衍生物以前已经显示出对蚊子传播的黄病毒的潜力,这表明了新药开发的途径.

研究的目的:

为了研究硫胺石墨衍生物作为DENV.的潜在抑制剂.
为了识别这些化合物的分子标.
在临床前小鼠模型中评估有前途的候选者的安全性.

主要方法:

使用基于细胞的抗病毒和细胞毒性测试对27种硫胺的查.
对候选物的DENV抑制 (EC50) 和化合物毒性 (CC50) 的确定.
通过监测肝脏和功能标志物 (ALT,Cr) 来评估C57BL/6小鼠中的化合物安全性.
使用计算和基于酶的测定来识别分子点.

主要成果:

两个化合物SC22和SC27显示出显著的DENV抑制,EC50值处于低微分子范围.
SC27表现出有利的治疗指数,CC50值明显高于EC50.
给小鼠施用SC22或SC27并没有提高ALT或Cr水平,这表明急性安全性良好.
计算和酶分析确定了NS5甲基转移酶的SAM结合部位作为SC27.7的潜在标.
在病毒复制的后期阶段,SC22的主要标被确定,尽管具体的分子仍未得到证实.

结论:

SC27是一种有前途的DENV抑制剂,向病毒甲基转移酶,具有进一步开发的潜力.
SC22也显示出抗病毒活性,其目标需要进一步阐明.
硫胺石代表了一类可行的化合物,用于开发新的登革热抗病毒疗法.

关键词:

石灰是一种的材料.登革热是因为登革热.黄类化合物黄类甲基转移酶的使用方法硫胺是什么?硫胺是什么?

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