Universidade Federal do Amazonas, Centro de Apoio Multidisciplinar, Central Analítica, Manaus, AM, Brasil.
Secretaria Municipal de Saúde, Prefeitura de Itabirito, Itabirito, MG, Brasil.
Mem Inst Oswaldo Cruz. 2020 Sep 30;115:e200207. doi: 10.1590/0074-02760200207. eCollection 2020.
Since the World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) to be a pandemic infection, important severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (nsp) have been analysed as promising targets in virtual screening approaches. Among these proteins, 3-chymotrypsin-like cysteine protease (3CLpro), also named main protease, and the RNA-dependent RNA polymerase (RdRp), have been identified as fundamental targets due to its importance in the viral replication stages.
To investigate, in silico, two of the most abundant flavonoid glycosides from Dysphania ambrosioides; a medicinal plant found in many regions of the world, along with some of the putative derivatives of these flavonoid glycosides in the human organism as potential inhibitors of the SARS-CoV-2 3CLpro and RdRp.
Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives.
Docking analysis, based on the crystal structure of 3CLpro and RdRp, indicated rutin, nicotiflorin, and their glucuronide and sulfate derivatives as potential inhibitors for both proteins. Also, the importance of the hydrogen bond and π-based interactions was evidenced for the presumed active sites.
Overall, these results suggest that both flavonoid glycosides and their putative human metabolites can play a key role as inhibitors of the SARS-CoV-2 3CLpro and RdRp. Obviously, further researches, mainly in vitro and in vivo experiments, are necessary to certify the docking results reported here, as well as the adequate application of these substances. Furthermore, it is necessary to investigate the risks of D. ambrosioides as a phytomedicine for use against COVID-19.
自世界卫生组织（WHO）宣布 2019 年冠状病毒病（COVID-19）为大流行感染以来，重要的严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）非结构蛋白（nsp）已被分析为虚拟筛选方法中的有前途的靶标。在这些蛋白质中，3-糜蛋白酶样半胱氨酸蛋白酶（3CLpro），也称为主要蛋白酶，以及 RNA 依赖性 RNA 聚合酶（RdRp），已被确定为基本靶标，因为它在病毒复制阶段很重要。
在计算机上研究来自 Dysphania ambrosioides 的两种最丰富的类黄酮糖苷；这种药用植物在世界许多地区都有发现，以及这些类黄酮糖苷在人体中的一些假定衍生物，作为 SARS-CoV-2 3CLpro 和 RdRp 的潜在抑制剂。
使用分子对接方法，预测槲皮素-3-O-芸香糖苷（芦丁）、山奈酚-3-O-芸香糖苷（野黄芩苷）及其葡萄糖醛酸和硫酸盐衍生物与 SARS-CoV-2 3CLpro 和 RdRp 的相互作用和结合亲和力。
基于 3CLpro 和 RdRp 的晶体结构的对接分析表明，芦丁、野黄芩苷及其葡萄糖醛酸和硫酸盐衍生物可能是这两种蛋白的抑制剂。此外，氢键和基于π的相互作用对于假定的活性部位的重要性得到了证明。
总的来说，这些结果表明，类黄酮糖苷及其假定的人体代谢物可以作为 SARS-CoV-2 3CLpro 和 RdRp 的抑制剂发挥关键作用。显然，需要进行更多的研究，主要是体外和体内实验，以验证这里报告的对接结果，以及这些物质的适当应用。此外，有必要研究作为 COVID-19 治疗药物的 Dysphania ambrosioides 的风险。
