摘要
利用分子对接技术探索三叶青中对新型冠状病毒(severe acute respiratory syndrome coronavirus2,SARS-CoV-2)有潜在抑制作用的活性化合物。通过检索国内外文献,搜集到162个三叶青化合物,同时与瑞德西韦、利托那韦和奈非那韦3个化学药建立配体库,并以3CL水解酶蛋白(3C-like protease protein, 3CLpro)、ACE2(angiotensin-converting enzyme 2)和SARS Mpro(severe acute respiratory syndrome main protein)为受体,采用Vina软件从三叶青中筛选出与3个靶蛋白有较好亲和作用的活性化合物。通过分子对接筛选出与3CLpro有较好亲和作用的化合物9个,与ACE2作用的化合物30个,与SARS Mpro作用的化合物11个。这些化合物与化药的结合能相当,它们主要属于黄酮、酚酸和二苯乙烯苷类化合物。上述化合物中Vitexin 2″-O-arabinofuranoside对3种蛋白质均有较好的亲和作用,亦有13个化合物可同时作用于2个不同的靶蛋白。采用PyMoL和LigPlot软件分析化合物与靶蛋白的结合模式及相互作用的氨基酸,发现所有化合物均可进入3个靶蛋白的活性中心,化合物结构中的羟基和羰基与活性中心的氨基酸形成了氢键作用和疏水作用。结果表明,推测三叶青中的黄酮、酚酸和二苯乙烯苷等三种类型的14个化合物可通过同时结合作用病毒的2或3个靶蛋白,从而可能发挥抗SARS-CoV-2感染作用。
This work was aimed to explore the potential active compounds of Tetrastigma hemsleyanum for the treatment of SARS-CoV-2(severe acute respiratory syndrome coronavirus 2) via molecular docking technology. A library ligand was established using 162 compounds from Tetrastigma hemsleyanum and 3 chemical drugs(remdesivir, ritonavir and nelfinavir) through retrieving. 3 CL hydrolase protein(3 C-like protease, 3 CLpro), ACE2(angiotensin-converting enzyme 2) and SARS Mpro(severe acute respiratory syndrome main protein) were downloaded as the receptor. Vina software was used to screen the candidate compounds, which might have affinity with three target proteins of SARS-CoV-2. Nine compounds exhibited lower binding energy with 3 CLpro, 30 compounds showed lower binding energy with ACE2, 11 compounds presented lower binding energy with SARS Mpro. The above compounds belong to flavonoid, phenolic acid and stibene glucoside, which had binding energy as low as 4 chemical drugs. Among the compounds, Vitexin 2’’-O-arabinofuranoside showed lowest binding energy within all the three target proteins, 12 compounds also exhibited lower binding energy with 2 target proteins. The binding pattern and interaction with amino acid between compounds and three target proteins were analyzed using PyMoL and LigPlot software. All compounds entered the active site of three target proteins, and formed hydrogen bonding and hydrophobic action with amino acids of the target protein. The present study speculated that 14 compounds of three types(flavonoid, phenolic acid and stibene glucoside) from Tetrastigma hemsleyanum might have the potential of anti-SARS-CoV-2 infections via combination with two or three target proteins.
作者
王芙蓉
王娟
陈泽南
刘兆玺
周爱珍
彭昕
WANG Furong;WANG Juan;CHEN Ze'nan;LIU Zhaoxi;ZHOU Aizhen;PENG Xin(Zhejiang Pharmaceutical College,Ningbo 315100,China;Ningbo Research Institute of Zhejiang University,Ningbo 315010,China)
出处
《生命的化学》
CAS
2021年第5期1068-1081,共14页
Chemistry of Life
基金
国家自然科学基金项目(81903743)
宁波市科技创新2025重大专项(2019B10008)
宁波市自然基金项目(2016A610241,2019A610370)
浙江医药高等专科学校基金项目(2019010)
浙江省中医药科技计划项目(2016ZB116)。
