摘要
2019年12月以来,由严重急性呼吸综合征冠状病毒2型(severe acute respiratory syndrome coronavirus-2,SARS-CoV-2)感染引起的新型冠状病毒肺炎(novel coronavirus disease 2019,COVID-19)在全球范围内流行和传播,具有较高的传染性、发病率和死亡率。目前,国内外仍缺乏特效且无明显副作用的治疗药物。基于COVID-19的特异性靶点(AXL、3CL pro、ACE2),利用高通量分子对接技术在TCMSP数据库中虚拟筛选潜在活性小分子,并从TCMSP、TCMIP和TCMID数据库中预测相应的潜在中药。结果显示,作用于AXL、3CL pro和ACE2的共靶点小分子有47个,包括萜类、生物碱类、黄酮类、醌类和苷类等,其中萜类所占比例最高。其中Chelidimerine与AXL和3CL pro的结合能力最强,可能是一种治疗COVID-19的潜在化合物。基于ADME和Lipinski规则,得到10个具有良好药代动力学特征的化合物。此外,预测获得了13味治疗COVID-19的高频中药。本实验获得的针对COVID-19的潜在活性分子(PAM)和潜在中药,可为后续的抗病毒活性研究、新药开发和临床应用提供有意义的参考。
In December 2019,a novel coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection was prevalent and transmitted worldwide,with high infectivity,morbidity and mortality.Nowadays,there is still a lack of therapeutic drugs with no obvious side effects.In this paper,based on multiple specific targets(AXL、3CL pro、ACE2)of COVID-19,we used high-throughput molecular docking technology to virtually screen compounds in TCMSP database,and the corresponding Chinese herbs were found from TCMSP,TCMIP and TCMID databases.The results showed that there were 47 co-target small molecules acting on AXL,3CL pro and ACE2.In addition,according to these structures,they were divided into terpenes,alkaloids,flavonoids,quinones,glycosides and others,and terpenes accounted for the highest proportion among them.Chelidimerine has the strongest binding ability with AXL and 3CL pro,and is considered to be a potential compound for the treatment of COVID-19.Based on ADME and Lipinski s Rules,we obtained 10 compounds with good pharmacokinetic characteristics.In addition,13 high-frequency Chinese herbs for the treatment of COVID-19 were predicted.In this experiment,the potential active molecules(PAM)and potential Chinese herbs for COVID-19 provided a meaningful reference for subsequent antiviral activity research,new drug development and clinical application.
作者
祁建宏
董芳旭
王轲
刘子铭
朱锦璐
QI Jianhong;DONG Fangxu;WANG Ke;LIU Ziming;ZHU Jinlu(College of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;College of Foreign languages,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Innovative Institute of Chinese Medicine and Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)
出处
《北京联合大学学报》
CAS
2022年第1期44-53,71,共11页
Journal of Beijing Union University
