从TCMSP中药数据库中筛选猴痘病毒胸苷酸激酶抑制剂  

Screening potential thymidylate kinase inhibitors from TCMSP database against monkeypox virus

作　　者：王育伟 田王琪 张蔚桐 汪一凡 靳晓杰 唐于平 董泰玮 WANG Yu-wei;TIAN Wang-qi;ZHANG Wei-tong;WANG Yi-fan;JIN Xiao-jie;TANG Yu-ping;DONG Tai-wei(College of Pharmacy,Shaanxi University of Chinese Medicine,Xi'an 712046,China;College of Pharmacy,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]陕西中医药大学药学院,西安712046 [2]甘肃中医药大学药学院,兰州730000

出　　处：《中国新药杂志》2023年第16期1668-1676,共9页Chinese Journal of New Drugs

基　　金：国家自然科学基金项目(82003653);陕西省自然科学基金项目(2021JQ-734)。

摘　　要：目的:运用虚拟筛选技术从中药数据库中筛选猴痘病毒胸苷酸激酶潜在的中药小分子抑制剂。方法:基于已公布的猴痘病毒胸苷酸激酶序列,利用同源模建技术构建猴痘病毒胸苷酸激酶三维结构,运用基于对接的虚拟筛选技术进行多轮筛选,包括高通量虚拟筛选、标准精度虚拟筛选、高精度虚拟筛选、Prime MMGBSA结合自由能筛选等。结果:筛选出了15个对猴痘病毒胸苷酸激酶具有潜在抑制活性的化合物,并分析了化合物MOL002468,MOL009538,MOL000416,MOL009237与胸苷酸激酶的结合模式,包括氢键、疏水相互作用、共轭和盐桥等受体-配体相互作用。结论:成功构建猴痘病毒胸苷酸激酶的虚拟筛选策略,发掘可用于预防、治疗猴痘病毒的药物,促进传统中药数据库的进一步开发和利用。Objective:To screen potential small-molecule inhibitors of monkeypox virus thymidylate kinase from traditional Chinese medicine databases using virtual screening technology.Methods:Based on the published monkeypox virus thymidylate kinase sequence,the three-dimensional structure of monkeypox virus thymidylate kinase was constructed using homology modeling technology,and multiple rounds of screening were performed using docking-based virtual screening technology,including high-throughput virtual screening,standard precision virtual screening,high precision virtual screening and Prime MMGBSA.Results:Fifteen compounds with potential inhibitory activity against monkeypox virus thymidylate kinase were obtained by screening.The binding modes of compounds MOL002468,MOL009538,MOL000416 and MOL009237 with thymidylate kinase were analyzed for receptor-ligand interactions including hydrogen bonding,hydrophobic interactions,conjugation and salt bridges.Conclusion:A virtual screening strategy for monkeypox virus thymidylate kinase was successfully constructed in order to discover new drugs that can be used to prevent and treat monkeypox virus,promoting further development and utilization of traditional Chinese medicine databases.

关 键 词：猴痘 胸苷酸激酶 分子对接 结合自由能 虚拟筛选 

分 类 号：R965.1[医药卫生—药理学]