Suleimen Yerlan M, Jose Rani A, Mamytbekova Gulnur K, Suleimen Raigul N, Ishmuratova Margarita Y, Dehaen Wim, Alsfouk Bshra A, Elkaeed Eslam B, Eissa Ibrahim H, Metwaly Ahmed M
Technopark Department, Kazakh University of Technology and Business, Nur-Sultan 010000, Kazakhstan.
The Laboratory of Engineering Profile of NMR Spectroscopy, Sh. Ualikhanov Kokshetau University, Kokshetau 020000, Kazakhstan.
Plants (Basel). 2022 Aug 8;11(15):2072. doi: 10.3390/plants11152072.
The phytochemical constituents of Jaub. & Spach (Family Polygonaceae) were studied for the first time. The study resulted in the isolation of the rare flavonol glycoside, kaempferol 3--(6″--acetyl)-glucoside,(K3G-A). The potential inhibitive activity of K3G-A toward SARS-CoV-2 was investigated utilizing several in silico approaches. First, molecular fingerprints and structural similarity experiments were carried out for K3G-A against nine co-crystallized ligands of nine proteins of SARS-CoV-2 to reveal if there is a structural similarity with any of them. The conducted studies showed the high similarity of K3G-A and remdesivir, the co-crystallized ligand of SARS-CoV-2 RNA-dependent RNA polymerase (PDB ID: 7BV2), RdRp. To validate these findings, a DFT study was conducted and confirmed the proposed similarity on the electronic and orbital levels. The binding of K3G-A against RdRp was confirmed through molecular docking studies exhibiting a binding energy of -27.43 kcal/mol, which was higher than that of remdesivir. Moreover, the RdRp-K3G-A complex was subjected to several MD studies at 100 ns that authenticated the accurate mode of binding and the correct dynamic behavior. Finally, in silico ADMET and toxicity evaluation of K3G-A was conducted and denoted the safety and the drug-likeness of K3G-A. In addition to K3G-A, two other metabolites were isolated and identified to be kaempferol (K) and β-sitosterol (β-S).
首次对蓼科植物Jaub. & Spach的植物化学成分进行了研究。该研究分离出了罕见的黄酮醇苷，山奈酚3 - (6″ - 乙酰基)-葡萄糖苷（K3G-A）。利用多种计算机模拟方法研究了K3G-A对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的潜在抑制活性。首先，针对K3G-A对SARS-CoV-2九种蛋白质的九种共结晶配体进行了分子指纹和结构相似性实验，以揭示其与其中任何一种是否存在结构相似性。所进行的研究表明，K3G-A与瑞德西韦具有高度相似性，瑞德西韦是SARS-CoV-2 RNA依赖性RNA聚合酶（PDB ID：7BV2）RdRp的共结晶配体。为了验证这些发现，进行了密度泛函理论（DFT）研究，并在电子和轨道水平上证实了所提出的相似性。通过分子对接研究证实了K3G-A与RdRp的结合，其结合能为-27.43千卡/摩尔，高于瑞德西韦。此外，对RdRp-K3G-A复合物进行了100纳秒的多次分子动力学（MD）研究，验证了准确的结合模式和正确的动力学行为。最后，对K3G-A进行了计算机模拟的药物代谢动力学、药物吸收、分布、代谢和排泄（ADMET）及毒性评估，表明K3G-A具有安全性和类药物性质。除了K3G-A外，还分离并鉴定出另外两种代谢产物，即山奈酚（K）和β-谷甾醇（β-S）。
