Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Mol Cell Probes. 2022 Oct;65:101847. doi: 10.1016/j.mcp.2022.101847. Epub 2022 Jul 14.
SARS-COV-2 stands as the source of the most catastrophic pandemic of this century, known as COVID-19. In this regard, we explored the effects of five Pistacia sp. active ingredients on the most crucial targets of SARS-COV-2, including 3CLpro, PLpro, RdRp, helicase, NSP15, and E protein. The results of molecular docking determined 1,2,3,4,6-pentagalloyl glucose (PG) as the most effective compound of Pistacia sp, which also confirmed its excellent binding affinities and stable interactions with helicase (-10.76 kcal/mol), RdRp (-10.19 kcal/mol), E protein (-9.51 kcal/mol), and 3CLpro (-9.47 kcal/mol). Furthermore, MD simulation was conducted to investigate the stability of all complexes throughout a 100 ns. In contrast to PLpro and NSP15, the analyses of Lennard-Jones potential, RMSDas, PCA, and SASA verified the ability of PG in forming stable and adequate interactions with RdRp, helicase, 3CLpro, and E protein due to standing as an effective inhibitor among the six targets, these data proposed the capability of PG, the most important compound of Pistacia sp., in inducing antiviral, anti-inflammatory, and antioxidant impacts on RdRp, helicase, 3CLpro, and E protein. Therefore, the possibility of inhibiting the replication and transcription processes and viral pathogenesis of SARS-COV-2 may be facilitated through the application of PG.
SARS-COV-2 是导致本世纪最严重大流行疾病 COVID-19 的罪魁祸首。在此背景下，我们探究了 5 种乳香属植物活性成分对 SARS-COV-2 关键靶点的影响，包括 3CLpro、PLpro、RdRp、解旋酶、NSP15 和 E 蛋白。分子对接结果表明，1,2,3,4,6-五没食子酰葡萄糖（PG）是乳香属植物中最有效的化合物，其与解旋酶（-10.76 kcal/mol）、RdRp（-10.19 kcal/mol）、E 蛋白（-9.51 kcal/mol）和 3CLpro（-9.47 kcal/mol）的结合亲和力和稳定性都非常出色。此外，还进行了 MD 模拟，以研究所有复合物在 100 ns 内的稳定性。与 PLpro 和 NSP15 不同，Lennard-Jones 势能、RMSDas、PCA 和 SASA 的分析结果证实，PG 能够与 RdRp、解旋酶、3CLpro 和 E 蛋白形成稳定且充分的相互作用，因为它是这 6 个靶点中有效的抑制剂。这些数据表明，PG 作为乳香属植物中最重要的化合物，有可能对 RdRp、解旋酶、3CLpro 和 E 蛋白发挥抗病毒、抗炎和抗氧化作用。因此，PG 的应用可能有助于抑制 SARS-COV-2 的复制和转录过程及病毒发病机制。
