背景:由严重急性呼吸道综合症冠状病毒2(SARS-CoV-2)引起的新型疾病的新毒株最近被世界卫生组织(WHO)宣布为大流行。该病毒在整个地球上导致显著的死亡率和发病率;因此,迫切需要新的治疗方法。最近沉积的SARS-CoV-2蛋白的晶体学结构引起了人们对大型数据库虚拟筛选的兴趣。
目的:在本研究中,我们通过基于共识的对接模拟,评估了IMPPAT植物化学数据库(8500种化合物)和SuperDRUG2数据集(4000种化合物)对SARS-CoV-2主要蛋白酶和解旋酶Nsp13的抑制能力.
方法:Glide和GOLD5.3在计算机模拟过程中实施。对每种蛋白质中的前10种抑制剂进行进一步的MM/GBSA计算以研究复合物的结合自由能。还进行了主要配体-蛋白质相互作用的分析。
结果:在对接模拟之后,我们获得了10种突出的植物化学物质和10种FDA批准的能够抑制Nsp5和Nsp13的药物。Delphinidin3,5,3'-三葡萄糖苷和hirsutinin3-O-(6-O-p-香豆酰基)葡萄糖苷分别表现出对Nsp5和Nsp13的最有利的结合自由能。
结论:结论:结果分析发现,与FDA批准的数据库相比,植物化学物质显示出增强的结合能力.
A new strain of a novel disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recently declared a pandemic by the World Health Organization (WHO). The virus results in significant mortality and morbidity across the planet; therefore, novel treatments are urgently required. Recently deposited crystallographic structures of SARS-CoV-2 proteins have ignited the interest in virtual screenings of large databases.
In the current study, we evaluated the inhibitory capacity of the IMPPAT phytochemical database (8500 compounds) and the SuperDRUG2 dataset (4000 compounds) in SARS-CoV-2 main protease and helicase Nsp13 through
consensus-based docking simulations.
Glide and GOLD 5.3 were implemented in the in silico process. Further MM/GBSA calculations of the top 10 inhibitors in each protein were carried out to investigate the binding free energy of the complexes. An analysis of the major ligand-protein interactions was also conducted.
After the docking simulations, we acquired 10 prominent phytochemicals and 10 FDAapproved drugs capable of inhibiting Nsp5 and Nsp13. Delphinidin 3,5,3\'-triglucoside and hirsutidin 3-O-(6-O-p-coumaroyl)glucoside demonstrated the most favorable binding free energies against Nsp5 and Nsp13, respectively.
In conclusion, the analysis of the results identified that the phytochemicals demonstrated enhanced binding capacities compared to the FDA-approved database.