Department of Organic & Bio-Molecular Chemistry, Chemical Engineering Institute, Ural Federal University, Mira St. 19, 620002 Yekaterinburg, Russia.
La Trobe Institute of Molecular Science, Plenty Rd & Kingsbury Dr., Bundoora, Melbourne, VIC 3086, Australia.
Mar Drugs. 2022 Mar 20;20(3):215. doi: 10.3390/md20030215.
The world is already facing the devastating effects of the SARS-CoV-2 pandemic. A disseminated mucormycosis epidemic emerged to worsen this situation, causing havoc, especially in India. This research aimed to perform a multitargeted docking study of marine-sponge-origin bioactive compounds against mucormycosis. Information on proven drug targets and marine sponge compounds was obtained via a literature search. A total of seven different targets were selected. Thirty-five compounds were chosen using the PASS online program. For homology modeling and molecular docking, FASTA sequences and 3D structures for protein targets were retrieved from NCBI and PDB databases. Autodock Vina in PyRx 0.8 was used for docking studies. Further, molecular dynamics simulations were performed using the IMODS server for top-ranked docked complexes. Moreover, the drug-like properties and toxicity analyses were performed using Lipinski parameters in Swiss-ADME, OSIRIS, ProTox-II, pkCSM, and StopTox servers. The results indicated that naamine D, latrunculin A and S, (+)-curcudiol, (+)-curcuphenol, aurantoside I, and hyrtimomine A had the highest binding affinity values of -8.8, -8.6, -9.8, -11.4, -8.0, -11.4, and -9.0 kcal/mol, respectively. In sum, all MNPs included in this study are good candidates against mucormycosis. (+)-curcudiol and (+)-curcuphenol are promising compounds due to their broad-spectrum target inhibition potential.
世界已经面临着 SARS-CoV-2 大流行的毁灭性影响。一种传播性的毛霉菌病疫情的出现，使情况恶化，尤其是在印度。本研究旨在对海洋海绵来源的生物活性化合物进行针对毛霉菌病的多靶点对接研究。通过文献检索获得了针对毛霉菌病的已证实药物靶点和海洋海绵化合物的信息。总共选择了七个不同的靶点。使用 PASS 在线程序选择了 35 种化合物。对于同源建模和分子对接，从 NCBI 和 PDB 数据库中检索了蛋白质靶标的 FASTA 序列和 3D 结构。使用 PyRx 0.8 中的 Autodock Vina 进行对接研究。此外，使用 IMODS 服务器对排名靠前的对接复合物进行分子动力学模拟。此外，使用瑞士 ADME、OSIRIS、ProTox-II、pkCSM 和 StopTox 服务器中的 Lipinski 参数进行药物样性质和毒性分析。结果表明，naamine D、latrunculin A 和 S、(+)-curcudiol、(+)-curcuphenol、aurantoside I 和 hyrtimomine A 的结合亲和力值最高，分别为-8.8、-8.6、-9.8、-11.4、-8.0、-11.4 和-9.0 kcal/mol。总之，本研究中包含的所有 MNPs 都是对抗毛霉菌病的候选药物。(+)-curcudiol 和 (+)-curcuphenol 是很有前途的化合物，因为它们具有广谱的靶标抑制潜力。
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