Yoosefian Mehdi, Esmaeili Arefeh, Abass Kasim Sakran
Department of Chemistry, Graduate University of Advanced Technology, Kerman, Iran.
Department of Physiology, Biochemistry, and Pharmacology, College of Veterinary Medicine, University of Kirkuk, Kirkuk, 36001, Iraq.
Sci Rep. 2025 Jul 28;15(1):27390. doi: 10.1038/s41598-025-13094-0.
Medicinal plants are considered rich sources of bioactive compounds with potential antiviral properties. In this study, the inhibitory effects of major phenolic compounds from Zingiber officinale (ginger), including gingerol, paradol, and shogaol, were investigated against the main protease (Mpro) of SARS-CoV-2, a critical enzyme for viral replication. The three-dimensional structures of the ligands and target protein were retrieved from PubChem and the RCSB Protein Data Bank, respectively. The pharmacokinetic and toxicity profiles of the compounds were assessed using the SwissADME and ProTox-II servers, which revealed favorable ADMET characteristics and a low toxicity profile for all selected compounds. Molecular docking was conducted using AutoDock 4.2 to predict the binding affinity and interaction modes of the ligands with Mpro. Among the tested compounds, shogaol exhibited the strongest binding affinity (- 9.95 kcal/mol) and formed stable hydrogen and hydrophobic interactions with key active site residues. To validate the docking results and further explore the stability of the ligand-protein complexes under physiological conditions, molecular dynamics (MD) simulations were performed for 500 ns using the GROMACS software. The MD analysis showed that the shogaol-Mpro complex had the lowest RMSD and consistent hydrogen bonding throughout the simulation, confirming its stable binding behavior. These findings suggest that ginger-derived phenolic compounds, particularly shogaol, may serve as promising candidates for the development of novel therapeutics targeting COVID-19 main protease.
药用植物被认为是具有潜在抗病毒特性的生物活性化合物的丰富来源。在本研究中，研究了姜（Zingiber officinale）中的主要酚类化合物，包括姜辣素、 paradol和姜烯酚，对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）主要蛋白酶（Mpro）的抑制作用，Mpro是病毒复制的关键酶。分别从PubChem和RCSB蛋白质数据库中检索配体和靶蛋白的三维结构。使用SwissADME和ProTox-II服务器评估化合物的药代动力学和毒性概况，结果显示所有选定化合物均具有良好的ADMET特性且毒性较低。使用AutoDock 4.2进行分子对接，以预测配体与Mpro的结合亲和力和相互作用模式。在所测试的化合物中，姜烯酚表现出最强的结合亲和力（-9.95千卡/摩尔），并与关键活性位点残基形成稳定的氢键和疏水相互作用。为了验证对接结果并进一步探索配体-蛋白质复合物在生理条件下的稳定性，使用GROMACS软件进行了500纳秒的分子动力学（MD）模拟。MD分析表明，姜烯酚-Mpro复合物在整个模拟过程中具有最低的均方根偏差（RMSD）和一致的氢键，证实了其稳定的结合行为。这些发现表明，姜衍生的酚类化合物，特别是姜烯酚，可能成为开发针对COVID-19主要蛋白酶的新型疗法的有前途的候选物。
