Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt.
Nat Prod Res. 2022 Nov;36(22):5724-5731. doi: 10.1080/14786419.2021.2019732. Epub 2021 Dec 27.
In the present study, a new secoiridoid glycoside lisianthoside II , along with seven known compounds were isolated from L. In-silico molecular docking and molecular dynamic simulation against SARS-CoV-2 Main protease (M) and RNA-dependent RNA polymerase (RdRp) were conducted. The affinity docking scores revealed that is the best bound ligand to M active site with binding energy of -14.9877 kcal/mol (RSMD = 1.16 Å), while was the highest against RdRp (-16.9572 kcal/mol, RMSD = 1.01 Å). Moreover, the molecular dynamic simulation revealed that with a (Δ) of -7.9 kcal/mol (RMSD value of 2.6 Å) and (RMSD value of 1.6 Å) and binding free energy (Δ) of -7.1 kcal/mol achieved the highest stability over 50 ns of MDS inside the M and RdRp enzyme's active site, respectively. Hence, the isolated compounds could be a good lead for development of new leads targeting COVID-19.
在本研究中，从莱菔硫烷中分离得到了一种新的裂环环烯醚萜苷——莱菔硫烷 II，以及另外七种已知化合物。对 SARS-CoV-2 主蛋白酶（M）和 RNA 依赖性 RNA 聚合酶（RdRp）进行了离体分子对接和分子动力学模拟。亲和对接评分显示，化合物 与 M 活性位点的结合能力最强，结合能为-14.9877 kcal/mol（RSMD = 1.16 Å），而 对 RdRp 的结合能力最强（-16.9572 kcal/mol，RMSD = 1.01 Å）。此外，分子动力学模拟显示，化合物 与 M 和 RdRp 酶活性位点的结合自由能（ΔG）分别为-7.9 kcal/mol（RMSD 值为 2.6 Å）和-7.1 kcal/mol（RMSD 值为 1.6 Å），稳定性最高，在 50 ns 的 MDS 内分别达到最高稳定性。因此，这些分离得到的化合物可能是针对 COVID-19 开发新型药物的良好先导化合物。
