目的 运用分子对接技术模拟预测TCMSP数据库中药成分对新型冠状病毒（SARS-CoV-2）3CL水解酶的作用。方法 基于SARS-CoV-2 3CL水解酶的PDB晶型结构（6LU7），构建虚拟靶标模型，以TCMSP数据库中的13 143个化合物为配体筛选对象，以6LU7原配体分子为对照，采用薛定谔2018软件，以Glide程序建立6LU7分子对接体系。然后以原配体分子的对接打分结果为阈值，口服生物利用度（OB）≥30%或类药性（DL）≥0.18为标准筛选候选化合物。最后建立“成分-药材-归经-功效”网络，对候选成分的主要药材归属和作用功效进行总结。结果 按照对接打分、OB、DL筛选标准，共筛选得到60个化合物。受体-配体相互作用结果显示，候选化合物主要与靶点蛋白的GLU166、GLY143、ASP187、CYS145、GLN189和LEU141等发生氢键作用。网络预测结果显示，所筛选化合物主要归属药材为甘草、桑白皮、满山红、虎杖和车前草等，肺脏是作用的关键靶器官，其作用功效以清热解毒、止咳祛痰、泻肺平喘等为主。结论 对TCMSP数据库化合物进行虚拟分子对接得到的结果为SARS-CoV-2 3CL水解酶抑制剂筛选提供了相关数据。

Objective To identify potential SARS-CoV-2 3CL protease inhibitors from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) by molecular docking approach. Methods To alternate extensive compounds experimental screening processes, a Computer-Aided Drug Design (CADD) based molecular docking technology was performed to explore existing drug repurposing possibilities. Molecular docking model with Schrodinger suit 2018 was used to evaluate the binding abilities between TCMSP 13 143 compounds and SARS-CoV-2 3CL protease receptor-binding domain (PBD ID 6LU7), which involving in mediating viral replication and transcription functions. According to the constructed docking system, potential compounds were screened according to docking score, oral bioavailability (OB), and drug-likeness (DL). At last, a compounds-herb-target organ-function network was constructed. Results Compared with 6LU7 original ligand docking score (-7.734), a total of 498 compounds were identified with lower docking score against 6LU7 targets. These compounds were further reduced to 60 high-priority compounds, based on OB (more than 30) and DL (more than 0.18). Meanwhile, these 60 compounds were found to interact with the amino acid residues (GLU166, GLY143, ASP187, CYS145, GLN189, LEU141, etc.) which were critically involved in the 6LU7 domain mainly by hydrogen-bonded interaction. The network exploring results revealed that these potential compounds were mainly attributed to Glycyrrhizae Radix et Rhizoma, Mori Cortex, Rhododendron dauricum, Polygoni Cuspidati Rhizoma et Radix, and Plantaginis Herba, etc., which associates with acute lung syndromes induced by SARS-CoV-2, with the effect of clearing heat and removing toxin, relieving cough and dispelling phlegm and lung-draining and relieving asthma. Conclusion Molecular docking method provides a useful tool for the screening of SARS-CoV-2 3CL protease inhibitors from TCMSP platform.

R285.5

2020年度咸阳市重点研发计划“新型冠状病毒肺炎疫情应急防治”科技专项；陕西省三秦学者创新团队；陕西省“特支计划”青年拔尖人才项目（陕组通字[2018]33号）