Blocking the interactions between human ACE2 and coronavirus spike glycoprotein by selected drugs: a computational perspective.

Environmental analysis, health and toxicology Pub Date : 2021-06-01 Epub Date: 2021-06-14 DOI:10.5620/eaht.2021010
Chidi Edbert Duru, Haruna Isiyaku Umar Umar, Ijeoma Akunna Duru, Uchechi Emmanuela Enenebeaku, Lynda Chioma Ngozi-Olehi, Christian Ebere Enyoh
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引用次数: 6

Abstract

The coronavirus disease of 2019 (COVID-19) has become a global pandemic with rapid rate of transmission and fatalities worldwide. Scientists have been investigating a host of drugs that may be rechanneled to fight this malaise. Thus, in this current computational study we carried out molecular docking experiments to assess the bridging potentials of some commercial drugs such as chloroquine, hydroxychloroquine, lopinavir, ritonavir, nafamostat, camostat, famotidine, umifenovir, nitazoxanide, ivermectin, and fluvoxamine at the interface between human ACE2 and the coronavirus spike glycoprotein complex. This is aimed at ascertaining the ability of these drugs to bridge and prevent the complexing of these two proteins. The crystal structure of human ACE2 and the coronavirus spike glycoprotein complex was retrieved from protein database, while the selected drugs were retrieved from PubChem data base. The proteins and drugs were prepared for docking using Cresset Flare software. The docking was completed via AutoDock Vina module in Python Prescription software. The best hit drugs with each receptor were selected and their molecular interactions were analyzed using BIOVIA's Discovery Studio 2020. The best hit compounds on the human ACE2 were the lopinavir (-10.1 kcal/mol), ritonavir (-8.9 kcal/mol), and nafamostat (-8.7 kcal/mol). Ivermectin, nafamostat, and camostat with binding energy values -9.0 kcal/mol, -7.8 kcal/mol, and -7.4 kcal/mol respectively were the hit drugs on the coronavirus spike glycoprotein. Nafamostat showed a dual bridging potential against ACE2 and spike glycoprotein, and could therefore be a promising lead compound in the prevention and control of this disease.

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通过选择药物阻断人类ACE2与冠状病毒刺突糖蛋白之间的相互作用:计算视角
2019年冠状病毒病(COVID-19)已成为全球大流行,在世界范围内传播速度快,死亡人数多。科学家们一直在研究一系列可以用来对抗这种不适的药物。因此,在当前的计算研究中,我们进行了分子对接实验,以评估一些商业药物如氯喹、羟氯喹、洛匹那韦、利托那韦、那莫他、卡莫他、法莫替丁、乌米诺韦、尼唑昔尼德、伊维菌素和氟伏沙明在人ACE2和冠状病毒刺突糖蛋白复合物界面上的桥接电位。这是为了确定这些药物的能力,以桥和防止这两个蛋白质的络合。人类ACE2和冠状病毒刺突糖蛋白复合物的晶体结构从蛋白质数据库中检索,所选药物从PubChem数据库中检索。利用Cresset Flare软件对蛋白质和药物进行对接制备。对接通过Python Prescription软件中的AutoDock Vina模块完成。选择每种受体的最佳药物,并使用BIOVIA的Discovery Studio 2020分析它们的分子相互作用。洛匹那韦(-10.1 kcal/mol)、利托那韦(-8.9 kcal/mol)和那莫他(-8.7 kcal/mol)对ACE2的影响最大。伊维菌素、那莫司他和卡莫司他的结合能分别为-9.0 kcal/mol、-7.8 kcal/mol和-7.4 kcal/mol,是对冠状病毒刺突糖蛋白的靶向药物。Nafamostat显示出对ACE2和刺突糖蛋白的双重桥接潜力,因此可能是预防和控制该疾病的有希望的先导化合物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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