桑辛素对新型冠状病毒主蛋白酶抑制作用的研究  

Study on Inhibition of SARS - CoV -2 Main Protease by Morusin

作　　者：张培红 赵洁 张欣欣 陈虹 闫成 苏彦雷 张晶[3] 孙殿兴 ZHANG Peihong;ZHAO Jie;ZHANG Xinxin;CHEN Hong;YAN Cheng;SU Yanlei;ZHANG Jing;SUN Dianxing(Hebei Province Academy of Chinese Medicine Sciences,Shijiazhuang 050030,Hebei,China;The 980th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army,Shijiazhuang 050082,Hebei,China;Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]河北省中医药科学院,河北石家庄050030 [2]联勤保障部队第九八〇医院,河北石家庄050082 [3]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050

出　　处：《中华中医药学刊》2023年第10期9-11,I0005,共4页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81672041);河北省卫生健康委员会重点科研攻关计划(20231303)。

摘　　要：目的 探讨桑辛素对新型冠状病毒主蛋白酶的抑制作用。方法 利用软件AutoDock将桑辛素与主蛋白酶晶体结构6LU7的活性位点进行分子对接;而后利用主蛋白酶荧光偏振筛选模型检验桑辛素对于新型冠状病毒主蛋白酶的抑制活性。结果 桑辛素与主蛋白酶活性位点具有较强的分子间相互作用,分子对接过程释放的自由能为-8.3 kcal/mol;在药理活性测试中,桑辛素在400、200、100、25μmol/L浓度对主蛋白酶的抑制率分别为45%、34%、8%、1%。结论 实验表明,桑辛素具有一定的主蛋白酶抑制活性。与既往报道的小分子黄酮类化合物相比,桑辛素对主蛋白酶的抑制活性明显增强,其原因可能为黄酮母核引入了脂溶性取代基进而增强了其与主蛋白酶活性位点处的结合能力相关,为黄酮母核类主蛋白酶抑制剂的结构优化提供参考。Objective To investigate the inhibitory effect of morusin on the main protease(Mpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).d Method The software AutoDock was used for molecular docking between morusin and the active site of the Mpro crystal structure 6LU7.Then,the Mpro fluorescence polarization screening model was used to test the effect of morusin on inhibiting the SARS-CoV-2 Mpro.s Results A strong intermolecular interaction was observed between morusin and the active site of Mpro,and the free energy released during the molecular docking process was-8.3 kcal/mol.In the pharmacological activity test,the inhibition rates of morusin on Mpro at the concentrations of 400μmol/L,200μmol/L,100μmol/L and 25μmol/L were 45%,34%,8%and 1%,respectively.n Conclusion The experiment shows that morusin has certain inhibitory activity on Mpro.Compared with that of the small-molecule flavonoid compounds previously reported by the author,the inhibitory activity of morusin on Mpro was significantly enhanced,which might be due to the introduction of fat-soluble sub-stituents in the flavonoid parent nucleus and the morusin’s subsequent enhanced binding ability to the active site of Mpro.This study provides a reference for the structural optimization of flavonoid parent nucleus Mpro inhibitors.

关 键 词：新型冠状病毒 主蛋白酶 荧光偏振筛选模型 桑辛素 抑制作用 

分 类 号：R282.71[医药卫生—中药学]