BACKGROUND 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. OBJECTIVES 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. METHODS 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. FINDINGS 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. MAIN CONCLUSIONS 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.

中文翻译：

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类黄酮苷及其推测的人类代谢产物，可能作为SARS-CoV-2主蛋白酶（Mpro）和RNA依赖性RNA聚合酶（RdRp）的潜在抑制剂

背景自世界卫生组织（WHO）宣布2019年冠状病毒病（COVID-19）为大流行性感染以来，重要的严重急性呼吸综合症冠状病毒2（SARS-CoV-2）非结构蛋白（nsp）已被分析为有希望的虚拟筛选方法中的目标。在这些蛋白质中，由于3-糜蛋白酶样半胱氨酸蛋白酶（3CLpro）（也称为主要蛋白酶）和RNA依赖性RNA聚合酶（RdRp），由于其在病毒复制阶段的重要性而被确定为基本靶标。目的在计算机上研究来自安非他命的两个最丰富的黄酮苷；在世界许多地区发现的药用植物，与这些类黄酮苷在人体内的某些推定衍生物一起，作为SARS-CoV-2 3CLpro和RdRp的潜在抑制剂。方法使用分子对接方法预测了槲皮素-3-O-芸苔苷（芦丁），山奈酚-3-O-芸苔苷（烟碱苷）及其一些与SARS-CoV-2 3CLpro和RdRp的相互作用和结合亲和力葡萄糖醛酸和硫酸盐衍生物。结果基于3CLpro和RdRp的晶体结构的对接分析表明，芦丁，烟碱及其葡萄糖醛酸和硫酸盐衍生物是这两种蛋白的潜在抑制剂。同样，对于假定的活性位点，证明了氢键和基于π的相互作用的重要性。主要结论总体而言，这些结果表明，类黄酮糖苷及其推定的人类代谢产物均可以作为SARS-CoV-2 3CLpro和RdRp的抑制剂发挥关键作用。显然，有必要进行进一步的研究，主要是体外和体内实验，以验证此处报道的对接结果以及这些物质的适当应用。此外，有必要研究作为杀草剂的D. ambrosioides对COVID-19的使用风险。