Abstract

Coronavirus Disease 2019 (COVID-19) has infected more than thirty five million people worldwide and caused nearly 1 million deaths as of October 2020. The microorganism causing COVID-19 was named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV). The aim of this study was to investigate the interactions of twenty-three phytochemicals belonging to different flavonoid subgroups with the receptor binding domain (RBD) of the spike glycoprotein of 2019-nCoV, and cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B and L (CatB/L)]. The compounds interacted more strongly with CatB and CatL than with the other proteins. Van der Waals and hydrogen bonds played an important role in the receptor-ligand interactions. As a result of RBCI (relative binding capacity index) analysis conducted to rank flavonoids in terms of their interactions with the target proteins, (-)-epicatechin gallate interacted strongly with all the proteins studied. The results obtained from molecular dynamics and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) methods also supported this data. According to Lipinski's rule of five, (-)-epicatechin gallate showed drug-likeness properties. Although this molecule is not capable of crossing the blood-brain barrier (BBB), it was concluded that (-)-epicatechin gallate can be evaluated as a candidate molecule in drug development studies against 2019-nCoV since it was not the substrate of P-gp (P-glycoprotein), did not inhibit any of the cytochrome Ps, and did not show AMES toxicity or hepatotoxicity on eukaryotic cells.

摘要

截至 2020 年 10 月，2019 年冠状病毒病 (COVID-19) 已感染全球超过 3500 万人，并造成近 100 万人死亡。导致 COVID-19 的微生物被命名为严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2 或2019新型冠状病毒）。本研究的目的是研究属于不同类黄酮亚组的 23 种植物化学物质与 2019-nCoV 刺突糖蛋白的受体结合域 (RBD) 和细胞蛋白酶 [跨膜丝氨酸蛋白酶 2 (TMPRSS2)、组织蛋白酶的相互作用。 B 和 L (CatB/L)]。这些化合物与 CatB 和 CatL 的相互作用比与其他蛋白质的相互作用更强烈。范德华力和氢键在受体-配体相互作用中起重要作用。(-) - 表儿茶素没食子酸酯与所有研究的蛋白质有强烈的相互作用。从分子动力学和分子力学泊松-玻尔兹曼表面积 (MM/PBSA) 方法获得的结果也支持了这一数据。根据 Lipinski 的五法则，(-) -表儿茶素没食子酸酯表现出药物相似性。尽管该分子不能穿过血脑屏障 (BBB)，但得出的结论是，(-) -表儿茶素没食子酸酯可作为针对 2019-nCoV 的药物开发研究的候选分子，因为它不是 P -gp（P-糖蛋白）不抑制任何细胞色素 Ps，并且对真核细胞没有显示 AMES 毒性或肝毒性。