Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp).
Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp).
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DOI：
10.1590/0074-02760200207
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发表时间：
2020
影响因子：
2.8
通讯作者：
de Souza ADL
中科院分区：
文献类型：
--
作者：
da Silva FMA;da Silva KPA;de Oliveira LPM;Costa EV;Koolen HH;Pinheiro MLB;de Souza AQL;de Souza ADL
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道综合征冠状病毒2（SARS-CoV-2）非结构蛋白（nsp）已被分析为虚拟筛选方法中有希望的靶标。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鉴定为基本靶标。 通过计算机模拟，研究在世界许多地区发现的一种药用植物-土荆芥中含量最丰富的两种黄酮苷，以及这些黄酮苷在人体内的一些推定衍生物，沿着作为SARS-CoV-2 3CLpro和RdRp的潜在抑制剂。 采用分子对接方法，预测了槲皮素-3-O-芸香糖苷（rutin）、山奈酚-3-O-芸香糖苷（nicotiflorin）及其葡萄糖醛酸苷和硫酸酯衍生物与SARS冠状病毒-2 3CLpro和RdRp的相互作用及其结合亲和力。 对接分析，基于晶体结构的3CLpro和RdRp，表明芦丁，烟草苷，和它们的葡萄糖醛酸苷和硫酸衍生物作为潜在的抑制剂的两种蛋白质。此外，氢键和基于π的相互作用的重要性被证明为推定的活性位点。 总的来说，这些结果表明，黄酮苷及其推定的人类代谢物都可以作为SARS-CoV-2 3CLpro和RdRp的抑制剂发挥关键作用。显然，进一步的研究，主要是在体外和体内实验，是必要的，以证明这里报道的对接结果，以及这些物质的适当应用。此外，有必要对D.土荆芥作为植物药用于对抗COVID-19。
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.
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DOI：
10.1016/j.jsps.2016.04.025
发表时间：
2017-02
期刊：
Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society
影响因子：
--
作者：
Ganeshpurkar A;Saluja AK
通讯作者：
Saluja AK
影响因子：
4
作者：
Negri EM;Piloto BM;Morinaga LK;Jardim CVP;Lamy SAE;Ferreira MA;D'Amico EA;Deheinzelin D
通讯作者：
Deheinzelin D
影响因子：
8.8
作者：
ul Qamar, Muhammad Tahir;Alqahtani, Safar M.;Chen, Ling-Ling
通讯作者：
Chen, Ling-Ling
影响因子：
3
作者：
Trott, Oleg;Olson, Arthur J.
通讯作者：
Olson, Arthur J.
影响因子：
3
作者：
Morris, Garrett M.;Huey, Ruth;Lindstrom, William;Sanner, Michel F.;Belew, Richard K.;Goodsell, David S.;Olson, Arthur J.
通讯作者：
Olson, Arthur J.