ABSTRACT

COVID-19 pandemic has poses urgent health challenge, and this project aims to identify potential inhibitors to combat this virus. We screened 198 bioactive compounds from five selected medicinal plants previously reported to be antiviral against SARS-CoV-2 protease and two co-receptors followed by molecular dynamics simulations. From the screened compounds, Astragalin demonstrated very strong molecular interactions with the molecular docking binding energies −8.5, −8.0, −7.6 kcal/mol for 6LU7, 6LZG, and 6VXX proteins of SARS-CoV-2, respectively. Hydrogen bonding interaction with the active site catalytic residue HIS-41 or CYS-145 of the main protease SARS-CoV-2 was observed. Binding free energies (ΔG_bind) from MM-GBSA after 50 ns MD simulations showed that Astragalin has the highest energy of −33.00 and −34.89 kcal/mol in complex with the main protease and spike glycoprotein of SARS-CoV-2, respectively. The study identifies Astragalin as a better inhibitor for the inactivation of COVID-19 and should be pursued as a potential drug candidate for this virus.

摘要

COVID-19大流行对健康构成了迫切的挑战，该项目旨在确定与这种病毒对抗的潜在抑制剂。我们从先前报道对SARS-CoV-2蛋白酶和两个共受体具有抗病毒作用的五种选择的药用植物中筛选了198种生物活性化合物，然后进行了分子动力学模拟。从筛选的化合物中，黄芪素对SARS-CoV-2的6LU7、6LZG和6VXX蛋白分别表现出非常强的分子相互作用，其分子对接结合能为-8.5，-8.0，-7.6 kcal / mol。观察到与主要蛋白酶SARS-CoV-2的活性位点催化残基HIS-41或CYS-145的氢键相互作用。结合自由能（ΔG_结合在50 ns的MD模拟后，来自MM-GBSA的）显示黄芪素与SARS-CoV-2的主要蛋白酶和峰值糖蛋白复合时的最高能量分别为-33.00和-34.89 kcal / mol。该研究确定了黄芪甲苷是使COVID-19失活的较好抑制剂，应作为该病毒的潜在候选药物进行研究。