Molecular docking and ADMET prediction of natural compounds towards SARS Spike glycoprotein-human angiotensin converting enzyme 2 and SARS-CoV-2 main protease

This in silico study evaluated the binding affinities of some natural products (resveratrol, xylopic acid, ellagic acid, kaempferol, and quercetin) to human angiotensin converting enzyme 2 and coronavirus (SARS-coV-2) main protease compared to chloroquine, an inhibitor known to prevent the cellular entry and replication of coronavirus. The respective binding energies of the selected natural compounds, and chloroquine were towards the proteins were computed using Pyrex Virtual Screening tool. The pharmacodynamic and pharmacokinetic attributes of the selected compounds were predicted using admetSAR. The molecular docking analysis showed the natural compoundshad the better scores towards the selected protein compared to chloroquinewith polar amino acid residues present at the binding sites.The predicted ADMET properties revealedthe natural products lower acute oral toxicity compared to chloroquine. The study provided evidence suggesting that the relatively less toxic natural compounds could be repositioned as anti-viral agents to prevent the entry and replication of SARS-CoV-2.

本虚拟仿真研究评估了若干天然产物（包括白藜芦醇、木犀草酸、鞣花酸、槲皮素和山奈酚）与人类血管紧张素转换酶2和冠状病毒（SARS-CoV-2）主要蛋白酶的结合亲和力，并与已知能防止冠状病毒细胞进入和复制的抑制剂氯喹进行了比较。利用Pyrex虚拟筛选工具计算了所选天然化合物与蛋白的结合能。采用admetSAR软件预测了所选化合物的药代动力学和药效学属性。分子对接分析显示，与氯喹相比，天然化合物在具有极性氨基酸残基的结合位点上的评分更高。预测的ADMET属性揭示，与氯喹相比，天然产物具有较低的急性口服毒性。该研究提供了证据，表明相对毒性较低的天然化合物有望重新定位为抗病毒药物，以防止SARS-CoV-2的进入和复制。