探索植物衍生小分子作为马尔堡病毒RNA结合蛋白活性抑制剂
Leena Hussein Bajrai1,2, Abdulrahman Abdullah Almalki3, Amaresh Kumar Sahoo4
1Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Journal of biomolecular structure & dynamics
|January 25, 2024
概括
研究人员使用in silico方法从药用植物中确定了四种潜在的马尔堡病毒VP35蛋白抑制剂. 这些化合物显示出有前途的结合,并可能导致新的抗病毒药物.
科学领域:
- 计算化学和药物发现
- 病毒学和传染病学.
- 植物化学和自然产品研究.
背景情况:
- 抗病毒药物开发需要识别病毒蛋白的强有力的抑制剂.
- 马尔堡病毒VP35蛋白的RNA结合活性是治疗干预的关键目标.
- 来自药用植物的天然产品是潜在药物候选物的丰富来源.
研究的目的:
- 为了确定马尔堡病毒VP35蛋白的RNA结合活性的潜在抑制剂.
- 探索选定的药用植物中的植物分子作为这些抑制剂的来源.
- 用计算方法评估已识别的化合物的结合相互作用和动态.
主要方法:
- 在 silico 药物发现方法包括大型植物分子库的虚拟选.
- 分子力学与一般化Born表面积 (MMGBSA) 分析用于化合物选择.
- 分子动力学 (MD) 模拟以评估与VP35蛋白的结合稳定性和相互作用.
主要成果:
- 四种化合物 (Kudzuisoflavone A,Miquelianin,Rutin,Protopseudohypericin) 被确定为潜在的抑制剂.
- 这些化合物是从药用植物中提取的:阿迪安图姆皮勒斯-维内里斯,超穿孔和普埃拉里亚山地.
- MD模拟证实了稳定的结合和有利的相互作用,结合能量优于myricetin.
结论:
- 鉴定的植物分子显示出作为马尔堡病毒VP35蛋白的抑制剂的显著潜力.
- 像A. capillus-veneris,H. perforatum和P. montana这样的药用植物是开发新型马尔堡病毒抗病毒药物的宝贵来源.
- 进一步的实验验证和优化对于将这些发现转化为临床应用至关重要.
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