黄酮类化合物抑制新型冠状病毒主蛋白酶的研究

A Study on Inhibition of SARS-CoV-2 Main Protease by Flavonoids

目的探讨部分黄酮类化合物对新型冠状病毒主蛋白酶的抑制作用。方法以奈玛特韦为阳性对照化合物,利用主蛋白酶荧光偏振法筛选模型检验黄酮类化合物橙皮素、木犀草素、染料木素、毛蕊异黄酮、芹菜素、根皮素、芹菜素-7-葡萄糖苷、染料木苷、染料木素-4'-葡萄糖苷和橙皮苷对于新型冠状病毒主蛋白酶的抑制活性。结果阳性对照物奈玛特韦在100、50、25μmol/L浓度对于主蛋白酶的抑制率分别为91%、76%和70%,而黄酮类化合物橙皮素、木犀草素、染料木素、毛蕊异黄酮、芹菜素、根皮素、芹菜素-7-葡萄糖苷、染料木苷、染料木素-4'-葡萄糖苷和橙皮苷在对应药物浓度均未表现出对主蛋白酶的有效抑制活性。结论上述黄酮类化合物在细胞水平具有抗新型冠状病毒的药理活性,其作用机理极可能为抑制新型冠状病毒RNA聚合酶,而并非抑制主蛋白酶,实验数据可为后续抗新型冠状病毒药物的研发提供思路和参考。

Objective To study the inhibitory effects of some flavonoids on the SARS-CoV-2 main protease.Methods Taking Nirmatrelvir as a positive control compound,the inhibitory activities of the flavonoids hesperidin,luteolin,genistein,calycosin,apigenin,phloretin,apigenin-7-glucoside,genistin,genistein-4'-glucopyranoside and hesperidin on the main protease of SARS-CoV-2 were tested using a sandwich-like fluorescence polarization assay(FP)screening model.Results The positive control Nirmatrelvir inhibited 91%,76%and 70%of the main protease at the concentrations of 100μM,50μM and 25μM,respectively,while the flavonoids hesperidin,luteolin,genistein,calycosin,apigenin,phloretin,apigenin-7-glucoside,genistein-4'-glucopyranoside and hesperidin did not show any effective inhibition activity against the main protease at the corresponding drug concentrations.Conclusion Flavonoids have pharmacological activities against SARS-CoV-2 at the cellular level,and their mechanism of action is most likely to be the inhibition of SARS-CoV-2 RNA polymerase,rather than the inhibition of the main protease.The experimental data can provide ideas and references for the development of subsequent anti-SARS-CoV-2 drugs.