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

作　　者：王绛辉 张晶[2] 段绪红 张丹 王鑫 常红 孙殿兴 苏彦雷 WANG Jianghui;ZHANG Jing;DUAN Xuhong;ZHANG Dan;WANG Xin;CHANG Hong;SUN Dianxing;SU Yanlei(Hebei Province Academy of Chinese Medicine Sciences,Shijiazhuang 050030,Hebei,China;Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;School of Pharmacy,Hebei University of Chinese Medicine,Shijiazhuang 050200,Hebei,China;Hebei Eye Hospital,Xingtai 054001,Hebei,China;The 980th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army,Shijiazhuang 050082,Hebei,China)

机构地区：[1]河北省中医药科学院,河北石家庄050030 [2]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 [3]河北中医学院药学院,河北石家庄050200 [4]河北省眼科医院,河北邢台054001 [5]联勤保障部队第九八〇医院,河北石家庄050082

出　　处：《中华中医药学刊》2023年第4期13-16,I0014,共5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科研基金项目(20191055);河北省中医药管理局科研计划项目(2020180,2016019)。

摘　　要：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.

关 键 词：新型冠状病毒 主蛋白酶 荧光偏振筛选模型 黄酮 药理活性 

分 类 号：R511[医药卫生—内科学] R259.631[医药卫生—临床医学]