发现基于糖的天然框架作为植物病原性病毒囊蛋白抑制剂,使用最先进的多重查策略
Jin-Hong Hu1, Zhen-Xing Li1, Yue Ding1
1State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.
International journal of biological macromolecules
|January 20, 2025
概括
研究人员开发了一种虚拟选方法,以识别针对烟草马赛克病毒 (TMV) 的天然化合物. 化合物A0和A4表现出强烈的结合,并有效地抑制了植物中的TMV复制,A4是有希望的负担得起的候选物.
科学领域:
- 生物化学 生物化学
- 植物病理学 植物病理学
- 计算化学计算化学
背景情况:
- 及时识别抗病毒抑制剂对于预防流行病爆发至关重要.
- 向病毒囊蛋白为开发新型抗病毒药物提供了一种策略.
- 基于天然产品的抑制剂是抗病毒药物发现的可持续方法.
研究的目的:
- 建立一个全面的多道选方法,用于识别烟草马赛克病毒 (TMV) 囊蛋白的抑制剂.
- 发现和评估基于糖的库中的天然化合物,这些化合物对TMV具有强大的抗病毒活性.
- 评估已识别的化合物作为植物TMV感染治疗剂的潜力.
主要方法:
- 一种多通道选方法,集成多个对接交叉验证,分子动力学模拟和密度函数理论计算.
- 利用基于糖的天然配体库对TMV体蛋白进行查.
- 生物活性评估,包括烟草植物的结合亲和力 (Kd) 和疗效 (EC50).
主要成果:
- 化合物A0和A4与现有的杀病毒剂宁南氨酸相比,对TMV囊蛋白具有更高的结合能力.
- A0和A4显著降低了TMV囊蛋白在转录水平的表达,抑制病毒生物合成和组装.
- A0和A4的抗TMV疗效与宁南素相当,A4被确定为一个具有成本效益的候选药物.
结论:
- 综合的虚拟查和生物活性验证策略有效地识别了针对性的抗病毒候选物.
- 化合物A0和A4显示出作为TMV新型抑制剂的显著潜力,需要进一步研究.
- 由于其可负担性和有效性,A4化合物代表了开发针对TMV的新策略的有希望的领先者.
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