2025年 05期

Multimodal Virtual Screening Method for Identifying Natural Molecule Drugs Targeting Inhibition of Coronavirus Nsp5 Protein


摘要(Abstract):

为了从天然分子数据库中筛选针对严重急性呼吸综合征冠状病毒(SARS-CoV-2)的Nsp5蛋白的潜在抑制剂,结合分子的一维、三维信息,开发了一种新的多模态虚拟筛选方法,筛选所得的候选化合物能够抑制Nsp5蛋白,可作为开发治疗冠状病毒病(COVID-19)药物的基础;通过带有随机失活机制的多加性回归树(DART)算法对SuperNatural数据库进行初步筛选,通过分子对接软件计算分子的对接得分,对得分排名前3位的分子进行分子动力学模拟验证动态结合效果。结果表明:所提出的方法中候选分子具备多样性,相较于单模态方法,候选分子具有更高的对接得分;分子动力学模拟结果显示,所选择的对接得分高的分子在靶标蛋白的动态结合位点具有良好的动态对接效果。

关键词(KeyWords):多模态虚拟筛选方法;严重急性呼吸综合征冠状病毒;Nsp5蛋白;天然分子;分子动力学模拟

基金项目(Foundation):国家自然科学基金项目(62371245)

作者(Author):王晨宇,许心怡,张豪,胡海峰,吴建盛

DOI:10.13349/j.cnki.jdxbn.20250704.002

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