Akash Shopnil, Mir Showkat Ahmad, Mahmood Sajjat, Hossain Saddam, Islam Md Rezaul, Mukerjee Nobendu, Nayak Binata, Nafidi Hiba-Allah, Bin Jardan Yousef A, Mekonnen Amare, Bourhia Mohammed
Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International, University, Dhaka, Bangladesh.
School of Life Sciences, Sambalpur University, Sambalpur, Odisha, India.
Front Microbiol. 2023 Jul 19;14:1206816. doi: 10.3389/fmicb.2023.1206816. eCollection 2023.
The alarming increase in tick-borne pathogens such as human is an existential threat to global public health. It is a protozoan parasitic infection transmitted by numerous species of the genus Babesia. Second, monkeypox has recently emerged as a public health crisis, and the virus has spread around the world in the post-COVID-19 period with a very rapid transmission rate. These two novel pathogens are a new concern for human health globally and have become a significant obstacle to the development of modern medicine and the economy of the whole world. Currently, there are no approved drugs for the treatment of this disease. So, this research gap encourages us to find a potential inhibitor from a natural source.
In this study, a series of natural plant-based biomolecules were subjected to in-depth computational investigation to find the most potent inhibitors targeting major pathogenic proteins responsible for the diseases caused by these two pathogens.
Among them, most of the selected natural compounds are predicted to bind tightly to the targeted proteins that are crucial for the replication of these novel pathogens. Moreover, all the molecules have outstanding ADMET properties such as high aqueous solubility, a higher human gastrointestinal absorption rate, and a lack of any carcinogenic or hepatotoxic effects; most of them followed Lipinski's rule. Finally, the stability of the compounds was determined by molecular dynamics simulations (MDs) for 100 ns. During MDs, we observed that the mentioned compounds have exceptional stability against selected pathogens.
These advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further and studies are necessary to validate their efficacy. Our research highlights the role of Dieckol and Amentoflavone as promising candidates for inhibiting both monkeypox and , demonstrating their multifaceted roles in the control of these pathogens.
诸如人巴贝斯虫等蜱传病原体的惊人增加对全球公共卫生构成了生存威胁。它是一种由多种巴贝斯属物种传播的原生动物寄生虫感染。其次，猴痘最近已演变成一场公共卫生危机，并且该病毒在新冠疫情后以非常快的传播速度在全球传播。这两种新型病原体是全球人类健康的新关注点，并已成为现代医学发展和全球经济的重大障碍。目前，尚无批准用于治疗该疾病的药物。因此，这一研究空白促使我们从天然来源寻找潜在的抑制剂。
在本研究中，对一系列基于天然植物的生物分子进行了深入的计算研究，以找到针对导致这两种病原体所致疾病的主要致病蛋白的最有效抑制剂。
其中，大多数选定的天然化合物预计会与对这些新型病原体复制至关重要的靶向蛋白紧密结合。此外，所有分子都具有出色的药物代谢动力学（ADMET）特性，如高水溶性、较高的人体胃肠道吸收率，且无任何致癌或肝毒性作用；它们中的大多数遵循Lipinski规则。最后，通过100纳秒的分子动力学模拟（MDs）确定了化合物的稳定性。在分子动力学模拟过程中，我们观察到上述化合物对选定病原体具有出色的稳定性。
这些先进的计算策略表明，包括二eckol和穗花杉双黄酮在内的11种先导化合物具有高效力、优异的类药物性质且无毒性。这些化合物对靶酶表现出强烈的结合亲和力，尤其是二eckol，其在分子动力学模拟过程中表现出卓越的稳定性。MM/PBSA方法证实了穗花杉双黄酮和二eckol具有良好的结合能。然而，需要进一步的体外和体内研究来验证它们的疗效。我们的研究突出了二eckol和穗花杉双黄酮作为抑制猴痘和人巴贝斯虫的有前景候选物的作用，证明了它们在控制这些病原体方面的多方面作用。
