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

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.