目的 基于超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-Q-TOF-MS)指纹图谱和分子对接技术,确定藿香正气水(Huoxiang Zhengqi Shui,HZS)抗新型冠状病毒(SARS-CoV-2)的潜在质量标志物(quality markers,Q-Marker)。方法 对27批HZS样品建立UPLC-Q-TOF-MS指纹图谱,结合化学计量学方法,筛选出HZS的差异性成分;以瑞德西韦为阳性对照,将HZS的差异性成分与SARS-CoV-2主蛋白酶(main protease,Mpro)进行分子对接,进一步确定HZS的潜在Q-Marker。结果 通过建立27批HZS样品的UPLC-Q-TOF-MS指纹图谱,标定了27种共有化合物;结合层次聚类分析(hierarchical clustering analysis,HCA)和主成分分析(principal component analysis,PCA),确定了其中14种共有化合物在27批HZS样品中具有较大的差异性,并鉴定出了橙皮苷、氧化前胡素、新比克白芷内脂、甜橙素、甘草酸、3,5,6,7,8,3',4'-七甲氧基黄酮、桔皮素、欧前胡素、珊瑚菜素9种差异性化合物;9种差异性化合物的分子对接结果显示,橙皮苷、氧化前胡素、新比克白芷内脂、甘草酸、欧前胡素、珊瑚菜素6种化合物能与SARS-CoV-2 Mpro的活性氨基酸结合,具有抑制SARS-CoV-2 Mpro的潜能,可作为HZS的潜在Q-Marker。结论 将UPLC-Q-TOF-MS指纹图谱、化学计量学分析和分子对接技术交叉使用,确定了HZS的潜在Q-Marker,该方法为药物成分鉴定、同一类药物成分差异性分析,及其功效研究方面提供一定参考。

Objective To screen the potential quality markers (Q-Marker) of anti-coronavirus of Huoxiang Zhengqi Shui (藿香正气水,HZS) based on the ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) fingerprints and molecular docking. Methods UPLC-Q-TOF-MS fingerprints and chemometric methods were employed to establish fingerprints and find out the difference between the peaks for the 27 batches of HZS samples.The SARS-CoV-2 main protease (Mpro) inhibition potential of the differential compounds among the 27 batches of HZS were further predicted by molecular docking with remdesivir as positive control. Results The UPLC-Q-TOF-MS fingerprints of 27 batches of HZS samples were set up with 27 common peaks.Combined with hierarchical clustering analysis (HCA) and principal component analysis (PCA),14 common peaks were determined as differential compounds,and nine of them were identified as hesperidin,oxypeucedanin,neobyakangelicol,sinensetin,glycyrrhizic acid,3,5,6,7,8,3',4'-heptamethoxyflavone,tangeretin,imperatorin and phellopterin.Molecular docking results showed that a total of six differential compounds were proven to have a certain inhibitory effect on SARS-CoV-2 Mpro,which can be used as potential Q-Marker of HZS,including hesperidin,oxypeucedanin,neobyakangelicol,glycyrrhizic acid,imperatorin and phellopterin.Conclusion The potential Q-Marker of HZS was determined by UPLC-Q-TOF-MS fingerprints,chemometric analysis and molecular docking.This method may provide a certain reference for the identification of various drug components,analysis of the differences of the same type drug components and pharmaceutical activity evaluation.

R283.6

北京市"科技助力经济2020"重点专项(SQ2020YFF0414333);2020年苏州市新型冠状病毒感染应急防治专项(XG56)