先进的虚拟查可以发现针对宿主和广泛的抗病毒药物
Garri Chilingaryan1, Roza Izmailyan2, Rafayela Grigoryan2
1Laboratory of Antiviral Drug Discovery, Institute of Molecular Biology of NAS, 0014, Yerevan, Armenia; Biocentric.AI, 0051, Yerevan, Armenia.
Antiviral research
|July 27, 2023
概括
先进的虚拟查发现了用于广泛抗病毒药物开发的人类二甲酸脱酶 (DHODH) 的新型抑制剂. Comp 19 显示出强大的抗病毒活性,并抑制了 DHODH,显示出新疗法的前景.
科学领域:
- 药用化学 医学化学
- 病毒学 病毒学
- 计算机化药物发现技术
背景情况:
- 人类二甲基酸脱酶 (DHODH) 是抗病毒药物开发的验证目标.
- 识别新的DHODH抑制剂对于对抗病毒感染至关重要.
研究的目的:
- 使用高级虚拟查 (AVS) 发现人类DHODH的新型抑制剂.
- 评估针对HSV-1的已识别化合物的抗病毒活性,并评估它们的作用机制.
主要方法:
- 使用AVS选495,118种化合物以确定潜在的DHODH抑制剂.
- 根据对接分数选择了28种新型化合物,并进行了针对HSV-1的体外抗病毒试验.
- 进行生物化学测试和分子动力学模拟,以表征最强大的抑制剂Comp 19.
主要成果:
- 鉴定了七种具有显著抗病毒作用的化合物对HSV-1,其中Comp 19是最强的 (IC50 = 1.1μM).
- Comp 19 证明了对人类 DHODH 的剂量依赖性抑制 (IC50 = 7.3 μM),并与该酶形成了稳定的复合物.
- Comp 19 具有广泛的抗病毒活性,并抑制了 THP-1 细胞中细胞因子的产生.
结论:
- AVS是发现具有广泛抗病毒潜力的新型DHODH抑制剂的有效策略.
- Comp 19 是一个有前途的化合物,可用于开发针对 DHODH.DH 的新抗病毒疗法.
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