The International Centre for Interdisciplinary Solutions on Antibiotics and Secondary Metabolites, Republican Collection of Microorganisms, Nur-Sultan 010000, Kazakhstan.
The Laboratory of Engineering Profile of NMR Spectroscopy, Sh. Ualikhanov Kokshetau University, Kokshetau 020000, Kazakhstan.
Molecules. 2022 Mar 1;27(5):1636. doi: 10.3390/molecules27051636.
A new flavonoid, Jusanin, () has been isolated from the aerial parts of . The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone. Being new in nature, the inhibition potential of has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between and , the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between and . Accordingly, molecular docking studies of against the target enzyme have been achieved and showed that bonded correctly in the protein's active site with a binding energy of -19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the M-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (), methyl-3-[S-hydroxyprenyl]-cumarate (), and β-sitosterol ().
从中分离得到一种新的类黄酮化合物 Jusanin。Jusanin 的化学结构通过 1D、2D NMR 和 HR-MS 光谱方法阐明为 5,2',4'-三羟基-6,7,5'-三甲氧基黄酮。由于其性质新颖，使用不同的计算技术估计了对 SARS-CoV-2 的抑制潜力。首先，对 Jusanin 进行了分子相似性和指纹研究，以对抗八种不同 SARS-CoV-2 必需蛋白的共结晶配体。研究表明，与 SARS-CoV-2 主蛋白酶（PDB ID：6W63）的共结晶配体 之间存在相似性。为了证实获得的结果，进行了 DFT 研究，并表明 之间的相似性（总能量、HOMO、LUMO、能隙和偶极矩）。因此，对靶酶进行了 Jusanin 的分子对接研究，结果表明 Jusanin 与靶酶的活性部位正确结合，结合能为-19.54 Kcal/mol。此外，还进行了 Jusanin 的虚拟 ADMET 以及对七种模型的毒性评估，表明 Jusanin 具有一般安全性并且类似于药物。最后，应用分子动力学模拟研究来研究 M-Jusanin 复合物的动态行为，并在 100 ns 时确认了正确的结合。除了 1 之外，还分离并鉴定了另外三种代谢物，分别为角鲨烯 A（）、3-[S-羟基异戊烯基]-香豆酸甲酯（）和 β-谷甾醇（）。
