Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan (USB), P.O.Box 98135- 674, Zahedan, Iran.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Box 71468-64685, Shiraz, Iran.
Recent Pat Biotechnol. 2024;18(4):316-331. doi: 10.2174/0118722083246773231108045238.
Since the COVID-19 outbreak in early 2020, researchers and studies are continuing to find drugs and/or vaccines against the disease. As shown before, medicinal plants can be very good sources against viruses because of their secondary compounds which may cure diseases and help in survival of patients. There is a growing trend in the filed patents in this field.
In the present study, we test and suggest the inhibitory potential of five herbal based extracts including 7α-acetoxyroyleanone, Curzerene, Incensole, Harmaline, and Cannabidiol with antivirus activity on the models of the significant antiviral targets for COVID-19 like spike glycoprotein, Papain-like protease (PLpro), non-structural protein 15 (NSP15), RNA-dependent RNA polymerase and core protease by molecular docking study.
The root was extracted, dried, and pulverized by a milling machine. The aqueous phase and the dichloromethane phase of the root extractive were separated by two-phase extraction using a separatory funnel. The separation was performed using the column chromatography method. The model of the important antivirus drug target of COVID-19 was obtained from the Protein Data Bank (PDB) and modified. TO study the binding difference between the studied molecules, the docking study was performed.
These herbal compounds are extracted from , and , respectively. The binding energies of all compounds on COVID-19 main targets are located in the limited area of 2.22-5.30 kcal/mol. This range of binding energies can support our hypothesis for the presence of the inhibitory effects of the secondary metabolites of mentioned structures on COVID-19. Generally, among the investigated herbal structures, Cannabidiol and 7α- acetoxyroyleanone compounds with the highest binding energy have the most inhibitory potential. The least inhibitory effects are related to the Curzerene and Incensole structures by the lowest binding affinity.
The general arrangement of the basis of the potential barrier of binding energies is in the order below: Cannabidiol > 7α-acetoxyroyleanone > Harmaline> Incensole > Curzerene. Finally, the range of docking scores for investigated herbal compounds on the mentioned targets indicates that the probably inhibitory effects on these targets obey the following order: main protease> RNA-dependent RNA polymerase> PLpro> NSP15> spike glycoprotein.
自 2020 年初 COVID-19 爆发以来，研究人员和研究工作一直在继续寻找针对该疾病的药物和/或疫苗。如前所述，药用植物可能是对抗病毒的非常好的来源，因为它们的次生化合物可能治愈疾病并帮助患者生存。该领域的专利申请呈增长趋势。
在本研究中，我们测试并提出了五种基于草药的提取物的抑制潜力，包括 7α-乙酰氧基罗勒酮、莪术烯、菖蒲脑、哈尔马林和具有抗病毒活性的大麻二酚，针对 COVID-19 的重要抗病毒靶点模型，如刺突糖蛋白、木瓜样蛋白酶 (PLpro)、非结构蛋白 15 (NSP15)、RNA 依赖性 RNA 聚合酶和核心蛋白酶进行分子对接研究。
根用粉碎机提取、干燥和粉碎。使用分液漏斗通过两相萃取法将根提取物的水相和二氯甲烷相分离。采用柱层析法进行分离。从蛋白质数据库 (PDB) 获得 COVID-19 的重要抗病毒药物靶点模型并进行修改。为了研究研究分子之间的结合差异，进行了对接研究。
这些草药化合物分别从 、 和 中提取。所有化合物在 COVID-19 主要靶点上的结合能都位于 2.22-5.30 kcal/mol 的有限区域内。这个结合能范围可以支持我们关于所提到结构的次生代谢物对 COVID-19 具有抑制作用的假设。一般来说，在所研究的草药结构中，大麻二酚和具有最高结合能的 7α-乙酰氧基罗勒酮化合物具有最强的抑制潜力。结合亲和力最低的 Curzerene 和 Incensole 结构的抑制作用最小。
结合能势垒基础的总体排列顺序如下：大麻二酚>7α-乙酰氧基罗勒酮>哈尔马林>菖蒲脑>莪术烯。最后，在所研究的草药化合物对所述靶标的对接得分范围表明，对这些靶标的可能抑制作用遵循以下顺序：主要蛋白酶>RNA 依赖性 RNA 聚合酶>PLpro>NSP15>刺突糖蛋白。
