Rutwick Surya U, Praveen N
Department of Life Sciences, CHRIST (Deemed To Be University), Hosur Road, Bengaluru, 560029 Karnataka India.
Virusdisease. 2021 Mar;32(1):46-54. doi: 10.1007/s13337-021-00683-6. Epub 2021 Mar 18.
SARS-CoV-2, the causative virus of the Corona virus disease that was first recorded in 2019 (COVID-19), has already affected over 110 million people across the world with no clear targeted drug therapy that can be efficiently administered to the wide spread victims. This study tries to discover a novel potential inhibitor to the main protease of the virus, by computer aided drug discovery where various major active phytochemicals of the plant Linn. namely 2-3-4 beta-Ecdysone, Bioquercetin, Biorobin, Boeravinone J, Boerhavisterol, kaempferol, Liriodendrin, quercetin and trans-caftaric acid were docked to SAR-CoV-2 Main Protease using Molecular docking server. The ligands that showed the least binding energy were Biorobin with - 8.17 kcal/mol, Bioquercetin with - 7.97 kcal/mol and Boerhavisterol with - 6.77 kcal/mol. These binding energies were found to be favorable for an efficient docking and resultant inhibition of the viral main protease. The graphical illustrations and visualizations of the docking were obtained along with inhibition constant, intermolecular energy (total and degenerate), interaction surfaces and HB Plot for all the successfully docked conditions of all the 9 ligands mentioned. Additionally the druglikeness of the top 3 hits namely Bioquercetin, Biorobin and Boeravisterol were tested by ADME studies and Boeravisterol was found to be a suitable candidate obeying the Lipinsky's rule. Since the main protease of SARS has been reported to possess structural similarity with the main protease of MERS, comparative docking of these ligands were also carried out on the MERS Mpro, however the binding energies for this target was found to be unfavorable for spontaneous binding. From these results, it was concluded that possess potential therapeutic properties against COVID-19.
The online version contains supplementary material available at 10.1007/s13337-021-00683-6.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是2019年首次发现的冠状病毒病（COVID-19）的致病病毒，已感染全球超过1.1亿人，目前尚无明确的靶向药物疗法可有效用于广大患者。本研究试图通过计算机辅助药物发现来寻找一种针对该病毒主要蛋白酶的新型潜在抑制剂，将植物Linn.的各种主要活性植物化学物质，即2-3-4β-蜕皮激素、生物槲皮素、生物洛宾、波希霍夫宁J、波希霍夫甾醇、山奈酚、鹅掌楸苷、槲皮素和反式咖啡酸，使用分子对接服务器与SARS-CoV-2主要蛋白酶进行对接。结合能最低的配体是生物洛宾，为-8.17千卡/摩尔，生物槲皮素为-7.97千卡/摩尔，波希霍夫甾醇为-6.77千卡/摩尔。发现这些结合能有利于有效对接并抑制病毒主要蛋白酶。获得了对接的图形说明和可视化结果，以及所有9种配体成功对接条件下的抑制常数、分子间能量（总和简并）、相互作用表面和氢键图。此外，通过药物代谢动力学（ADME）研究测试了排名前三的命中物生物槲皮素、生物洛宾和波希霍夫甾醇的类药性，发现波希霍夫甾醇符合Lipinski规则，是一个合适的候选物。由于据报道SARS的主要蛋白酶与中东呼吸综合征（MERS）的主要蛋白酶具有结构相似性，还对这些配体在MERS Mpro上进行了比较对接，然而发现该靶点的结合能不利于自发结合。从这些结果得出结论，其具有针对COVID-19的潜在治疗特性。
在线版本包含可在10.1007/s13337-021-00683-6获取的补充材料。
