Herlina Tati, Akili Abd Wahid Rizaldi, Nishinarizki Vicki, Hardianto Ari, Latip Jalifah
Department of Chemistry, Universitas Padjadjaran, Jatinangor, West Java, Indonesia.
Department of Chemical Sciences, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.
Adv Appl Bioinform Chem. 2024 May 14;17:61-70. doi: 10.2147/AABC.S454961. eCollection 2024.
This study aimed to screen potential drug candidates from the flavonoids of the genus for the Corona Virus Disease 2019 (COVID-19) treatment.
A comprehensive screening was conducted on the structures of 473 flavonoids derived from the genus , focusing on their potential toxicity and pharmacokinetic profiles. Subsequently, flavonoids that were non-toxic and possessed favorable pharmacokinetic properties underwent further analysis to explore their interactions with the angiotensin-converting enzyme 2 (ACE2) receptor, employing molecular docking and molecular dynamics simulations.
Among 473 flavonoids, 104 were predicted to be safe from being mutagenic, hepatotoxic, and inhibitors of the human ether-a-go-go-related gene (hERG). Among these 104 flavonoids, 18 compounds were predicted not to be substrates of P-glycoprotein (P-gp). Among these 18 flavonoids, gangetinin () and erybraedin D () exhibit low binding affinities and root mean square deviation (RMSD) values, indicating stable binding to the ACE2 receptor. The physicochemical attributes of compounds 310 and 471 suggest that they possess drug-like properties.
Gangetinin () and erybraedin D () may serve as promising candidates for COVID-19 treatment due to their potential to inhibit the ACE2-RBD interaction. This warrants further investigation into their inhibitory effects on ACE2-RBD binding through in vitro experiments.
本研究旨在从该属黄酮类化合物中筛选潜在的药物候选物，用于治疗2019冠状病毒病（COVID-19）。
对该属473种黄酮类化合物的结构进行了全面筛选，重点关注其潜在毒性和药代动力学特征。随后，对无毒且具有良好药代动力学性质的黄酮类化合物进行进一步分析，采用分子对接和分子动力学模拟来探索它们与血管紧张素转换酶2（ACE2）受体的相互作用。
在473种黄酮类化合物中，预测有104种对致突变、肝毒性和人类醚-去极化相关基因（hERG）抑制作用安全。在这104种黄酮类化合物中，预测有18种化合物不是P-糖蛋白（P-gp）的底物。在这18种黄酮类化合物中，gangetinin（）和erybraedin D（）表现出低结合亲和力和均方根偏差（RMSD）值，表明与ACE2受体的结合稳定。化合物310和471的物理化学属性表明它们具有类药物性质。
Gangetinin（）和erybraedin D（）可能是有前景的COVID-19治疗候选物，因为它们具有抑制ACE2-RBD相互作用的潜力。这值得通过体外实验进一步研究它们对ACE2-RBD结合的抑制作用。
