基于虚拟筛选方法从中药中发现SARS-CoV-2抑制剂

Discovery of SARS-CoV-2 Inhibitor from Traditional Chinese Medicine Based on Virtual Screening

主蛋白酶(Mpro)在SARS-CoV-2病毒自我复制过程中发挥重要作用,以蛋白酶Mpro为靶标的药物可以有效地治疗SARS-CoV-2病毒感染.因此,本研究对中药数据库TCMD进行虚拟筛选,筛选得到的化合物满足Lipinski规则与Veber规则,且通过TOPKAT预测,筛选得到的化合物具有良好的成药性.研究分子对接下的互作模式以及通过自由结合能验证复合物体系的稳定性.结果显示,化合物1(ZINC33830770,灵芝属三萜类化合物)和化合物4(ZINC1335889,杭菊中的不饱和脂肪酸异丁基酰胺)与阳性对照药物Talampicillin类似,在蛋白酶Mpro的活性口袋中,均表现出较强的亲和力以及稳定性.因此化合物1和化合物4可以通过抑制蛋白酶Mpro对COVID-19发挥潜在的防治作用.

The main protease(Mpro)of the SARS-CoV-2 plays an important role in the self-replication process,and drugs targeting the main protease can treat SARS-CoV-2 infections.Therefore,it was conducted a virtual screening on the traditional Chinese medicine database:TCMD,and the compounds obtained by the screening meet the Lipinski rule and the Veber rule,and the compounds obtained by the TOPKAT prediction.The compounds obtained by the screening have good pharmaceutical properties.Studying the interaction mode under molecular docking and verifying the stability of the complex system through free binding energy.The results showed that the compound 1(ZINC33830770,triterpenes from Ganoderma lucidum)and the compound 4(ZINC13358899,isobutylamides of unsaturated fatty acids from chrysanthemum morifolium)were confirmed to be similar to the positive control drug Talampicillin,shows strong affinity and stability in the active pocket of the main protease.Therefore,compound 1 and compound 4 can play a potential preventive effect on COVID-19 by inhibiting the Mpro.