使用蛋白质-蛋白质相互作用网络对潜在宿主蛋白质针对Flaviviridae的目标进行解码.
Jaya Vasavi Pamidimukkala1, Bharath Raj Parthasarathy1, Sanjib Senapati1
1Department of Biotechnology and BJM School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India.
International journal of biological macromolecules
|April 18, 2025
概括
这项研究确定了热,寨卡和C型肝炎等Flaviviridae病毒的常见可用药物宿主目标,并提出了可重复使用的药物,为广泛的抗病毒疗法提供了基础.
科学领域:
- 病毒学 病毒学
- 计算生物学 计算生物学
- 药物发现 药物发现 药物发现
背景情况:
- 弗拉维病毒病毒 (登革热,寨卡病毒,C型肝炎) 导致全球严重的健康问题.
- 了解病毒与宿主之间的相互作用对于确定治疗点至关重要.
- 组织特异性相互作用可以揭示新的药物点和重新利用机会.
研究的目的:
- 为Flaviviridae构建一个全面的病毒-人类互动组.
- 为了识别这些病毒利用的可用药物的宿主蛋白点.
- 为广泛的抗病毒疗法提出潜在的可重用药物.
主要方法:
- 多步计算方法将病毒-宿主蛋白-蛋白相互作用 (PPI) 与组织特异性基因表达相结合.
- 药物目标预测分析.
- 蛋白质 - 配体对接和分子动力学 (MD) 模拟.
主要成果:
- 已识别的可使用药物的蛋白质:CCNA2 (PBMC),EIF2S2,CDK7,CARS (肝脏).
- 拟议的可重复使用的药物:塔莫西芬,西洛利木斯,恩特雷克提尼布,L-氨酸.
- 通过对接和MD模拟验证了复杂稳定性.
结论:
- 在DENV,ZIKV和HCV感染中存在常见的可用药物的宿主目标.
- 这些发现支持开发针对Flaviviridae的统一治疗策略.
- 这项研究为新型广谱抗病毒药物开发提供了基础.
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