自然存在的伊索哈姆尼丁糖化物作为潜在的抗流感病毒剂:抗病毒和分子对接研究
Andrey Bogoyavlenskiy1, Irina Zaitseva1, Pavel Alexyuk1
1Research and Production Center for Microbiology and Virology, Almaty 050010, Kazakhstan.
ACS omega
|December 25, 2023
概括
来自Persicaria物种的新型伊索拉姆尼丁糖化物对流感有强大的抗病毒活性. 化合物5是前临床开发的有希望的候选者,因为它强烈抑制病毒复制和血凝素结合.
科学领域:
- 自然产品 化学 化学
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
背景情况:
- 流感病毒感染对全球健康构成重大负担,需要开发新型抗病毒疗法.
- 现有的抗病毒药物面临诸如耐药性和副作用等挑战,推动寻找替代治疗方法.
研究的目的:
- 从Persicaria物种中分离和表征异胺基化物.
- 评估这些化合物的抗病毒潜力在体外和体内对抗流感病毒.
- 阐明最强效化合物的作用机制.
主要方法:
- 使用染色学技术净化八种异胺基化物.
- 通过核磁共振 (NMR) 光谱学和质谱学 (MS) 进行表征.
- 在体外抗病毒检测 (EC50测定),胚胎体内研究,分子对接和分子动力学模拟.
主要成果:
- 化合物5表现出最强大的流感病毒抑制 (EC50:1.2-1.3μM),超过了像oseltamivir.vir这样的标准药物.
- 分子对接表示化合物5对病毒蛋白具有最强的结合亲和力 (-10.7 kcal/mol).
- 化合物1,5和6有效抑制病毒复制,而化合物5对血凝素的潜力比神经aminidase更大.
结论:
- 伊索哈姆尼丁糖化物,特别是化合物5,显示出作为新型抗流感剂的巨大潜力.
- 化合物5的机制涉及抑制病毒繁殖,并可能向血凝素.
- 对化合物5进行进一步的临床前评估是有必要的,以使其成为一种流感治疗药物.
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