基于分子对接技术的安宫牛黄丸治疗新型冠状病毒肺炎作用机制研究

Mechanism of Angong Niuhuang Pills in the Treatment of Coronavirus Disease 2019 Based on Molecular Docking Technology

目的基于分子对接技术探讨安宫牛黄丸中的有效化学成分与血管紧张素转换酶2(ACE2)结合的亲和力,以及其治疗新型冠状病毒肺炎(COVID-19)的作用机制。方法采用计算机检索TCMSP数据库中安宫牛黄丸中药材化学成分,从PDB数据库中下载ACE2的晶体结构,采用AutoDuck Vina 1.1.2软件对接其成分与ACE2。结果共检索到561个中药材化学成分,得到有效化学成分88个,文献补充13个,最终纳入101个。分子对接结果显示,安宫牛黄丸所有成分与ACE2的结合能均低于-5 kcal/mol,亲和力最好的3个成分为黄芩中baicalin(-9.9 kcal/mol)、黄连中corchoroside A_qt(-9.3 kcal/mol)、栀子中sudanⅢ(-9.3 kcal/mol),主要结合方式为与ACE2蛋白的活性区域形成氢键。结论安宫牛黄丸与ACE2蛋白的结合活性较强,具有治疗COVID-19的潜力。其作用机制可能为促进组织中ACE2表达,从而达到舒张血管、降低血管及细胞膜的通透性、抗增殖、抗氧化应激、抗血栓等作用。

Objective To explore the binding affinity of the active chemical components in Angong Niuhuang Pills and angiotensin-converting enzyme-2(ACE2)based on the molecular docking technology,and the mechanism of Angong Niuhuang Pills in the treatment of coronavirus disease 2019(COVID-19).Methods The chemical components of Chinese herbal medicine of Angong Niuhuang Pills in TCMSP database were searched,the crystal structure of ACE2 was downloaded from PDB database,and the components were docked with ACE2 by AutoDuck Vina 1.1.2 software.Results A total of 561 chemical components of Chinese herbal medicine were searched,including 88 effective chemical components,and 13 chemical components were supplemented by the literature,thus 101 chemical components were finally included.The results of molecular docking showed that the binding energy of all components of Angong Niuhuang Pills and ACE2 was lower than-5 kcal/mol,and the three components with the best affinity were baicalin in Scutellariae Radix(-9.9 kcal/mol),corchoroside A_qt in Coptidis Rhizoma(-9.3 kcal/mol)and sudanⅢin Gardeniae Fructus(-9.3 kcal/mol),the main binding mode was to form the hydrogen bond with the active region of ACE2 protein.Conclusion Angong Niuhuang Pills have strong binding activity with ACE2 protein,and it has the potential to treat COVID-19.The mechanism may promote the expression of ACE2 in the tissue,thereby achieving vasodilation,reducing the permeability of vascular and cell membrane,anti-proliferation,anti-oxidative stress and antithrombotic and so on.