Angourani Hossein Rabbi, Zarei Armin, Moghadam Maryam Manafi, Ramazani Ali, Mastinu Andrea
Research Institute of Modern Biological Techniques (RIMBT), University of Zanjan, Zanjan 45371-38791, Iran.
Department of Chemistry, Faculty of Science, University of Zanjan, Zanjan 45371-38791, Iran.
Life (Basel). 2023 Jan 30;13(2):378. doi: 10.3390/life13020378.
In this study, phytochemicals extracted from three different Achillea genera were identified and analyzed to be screened for their interactions with the SARS-CoV-2 main protease. In particular, the antiviral potential of these natural products against the SARS-CoV-2 main protease was investigated, as was their effectiveness against the SARS-CoV-1 main protease as a standard (due to its high similarity with SARS-CoV-2). These enzymes play key roles in the proliferation of viral strains in the human cytological domain. GC-MS analysis was used to identify the essential oils of the Achillea species. Chemi-informatics tools, such as AutoDock 4.2.6, SwissADME, ProTox-II, and LigPlot, were used to investigate the action of the pharmacoactive compounds against the main proteases of SARS-CoV-1 and SARS-CoV-2. Based on the binding energies of kessanyl acetate, chavibetol (m-eugenol), farnesol, and 7-epi-β-eudesmol were localized at the active site of the coronaviruses. Furthermore, these molecules, through hydrogen bonding with the amino acid residues of the active sites of viral proteins, were found to block the progression of SARS-CoV-2. Screening and computer analysis provided us with the opportunity to consider these molecules for further preclinical studies. Furthermore, considering their low toxicity, the data may pave the way for new in vitro and in vivo research on these natural inhibitors of the main SARS-CoV-2 protease.
在本研究中，对从三种不同的蓍属植物中提取的植物化学物质进行了鉴定和分析，以筛选它们与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）主要蛋白酶的相互作用。具体而言，研究了这些天然产物对SARS-CoV-2主要蛋白酶的抗病毒潜力，以及它们作为标准对SARS-CoV-1主要蛋白酶的有效性（由于其与SARS-CoV-2高度相似）。这些酶在人类细胞学领域的病毒株增殖中起关键作用。气相色谱-质谱联用（GC-MS）分析用于鉴定蓍属植物的精油。利用化学信息学工具，如AutoDock 4.2.6、SwissADME、ProTox-II和LigPlot，研究了具有药理活性的化合物对SARS-CoV-1和SARS-CoV-2主要蛋白酶的作用。基于乙酸开散尼酯、异丁香酚（间丁香酚）、法尼醇和7-表-β-桉叶醇的结合能，它们定位于冠状病毒的活性位点。此外，发现这些分子通过与病毒蛋白活性位点的氨基酸残基形成氢键，阻断SARS-CoV-2的进展。筛选和计算机分析为我们提供了将这些分子用于进一步临床前研究的机会。此外，考虑到它们的低毒性，这些数据可能为对这些SARS-CoV-2主要蛋白酶天然抑制剂的新的体外和体内研究铺平道路。
