School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, Ireland.
Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara, 06100, Turkey.
J Mol Model. 2021 Nov 3;27(11):341. doi: 10.1007/s00894-021-04963-2.
From the beginning of pandemic, more than 240 million people have been infected with a death rate higher than 2%. Indeed, the current exit strategy involving the spreading of vaccines must be combined with progress in effective treatment development. This scenario is sadly supported by the vaccine's immune activation time and the inequalities in the global immunization schedule. Bringing the crises under control means providing the world population with accessible and impactful new therapeutics. We screened a natural product library that contains a unique collection of 2370 natural products into the binding site of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M). According to the docking score and to the interaction at the active site, three phenylethanoid glycosides (forsythiaside A, isoacteoside, and verbascoside) were selected. In order to provide better insight into the atomistic interaction and test the impact of the three selected compounds at the binding site, we resorted to a half microsecond-long molecular dynamics simulation. As a result, we are showing that forsythiaside A is the most stable molecule and it is likely to possess the highest inhibitory effect against SARS-CoV-2 M. Phenylethanoid glycosides also have been reported to have both protease and kinase activity. This kinase inhibitory activity is very beneficial in fighting viruses inside the body as kinases are required for viral entry, metabolism, and/or reproduction. The dual activity (kinase/protease) of phenylethanoid glycosides makes them very promising anit-COVID-19 agents.
从疫情开始以来，已有超过 2.4 亿人感染，死亡率超过 2%。事实上，目前涉及疫苗传播的退出策略必须结合有效的治疗方法的开发进展。这种情况令人遗憾地得到了疫苗免疫激活时间和全球免疫接种时间表不平等的支持。控制危机意味着为世界人口提供可及且有效的新型治疗方法。我们筛选了一个天然产物库，其中包含 2370 种天然产物的独特集合，进入了严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）主蛋白酶（M）的结合位点。根据对接评分和活性部位的相互作用，选择了三种苯乙醇苷（连翘苷 A、异獐牙菜苷和毛蕊花糖苷）。为了更深入地了解原子相互作用，并测试三种选定化合物在结合部位的影响，我们进行了半微秒长的分子动力学模拟。结果表明，连翘苷 A 是最稳定的分子，它很可能对 SARS-CoV-2 M 具有最高的抑制作用。苯乙醇苷也被报道具有蛋白酶和激酶活性。这种激酶抑制活性在体内对抗病毒非常有益，因为激酶是病毒进入、代谢和/或繁殖所必需的。苯乙醇苷的双重活性（激酶/蛋白酶）使它们成为非常有前途的抗 COVID-19 药物。
