Drug Discovery and Multi-Omics Laboratory, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam 603103, Tamil Nadu, India.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Molecules. 2023 Oct 6;28(19):6955. doi: 10.3390/molecules28196955.
Contact lens-mediated microbial keratitis caused by and provokes corneal damage and vision loss. Recently, natural phytochemicals have become complementary medicines for corneal destruction. Herein, we aimed to identify multi-targeting -derived phytochemicals capable of inhibiting bacterial and host targets of keratitis through ADME (absorption, distribution, metabolism, and excretion), docking, molecular dynamics (MD) simulation, MMGBSA (molecular mechanics generalized Born surface area) and density functional theory (DFT) investigations. An extensive literature search revealed ExoU, ExoS, ExoT, ExoY, and PLY as virulent bacterial targets. Simultaneously, differential gene expression (DGE) and pathway enrichment analysis-specified host transcription factor (SPI1) influences keratitis pathogenesis. Molecular docking analysis uncovered aloeresin-A as a promising inhibitor against bacterial and host targets, demonstrating strong binding energies ranging from -7.59 to -6.20 kcal/mol. Further, MMGBSA and MD simulation analysis reflect higher binding free energies and stable interactions of aloeresin-A with the targets. In addition, DFT studies reveal the chemical reactiveness of aloeresin-A through quantum chemical calculations. Hence, our findings show aloeresin-A to be a promising candidate for effectively inhibiting keratitis. However, additional research is imperative for potential integration into lens care solutions.
接触镜介导的由 和 引起的微生物角膜炎会引起角膜损伤和视力丧失。最近，天然植物化学物质已成为治疗角膜破坏的补充药物。在此，我们旨在通过 ADME（吸收、分布、代谢和排泄）、对接、分子动力学（MD）模拟、MMGBSA（分子力学广义 Born 表面积）和密度泛函理论（DFT）研究，鉴定出能够抑制细菌和角膜炎宿主靶点的多靶标衍生植物化学物质。广泛的文献检索揭示了 ExoU、ExoS、ExoT、ExoY 和 PLY 是毒力细菌靶点。同时，差异基因表达（DGE）和途径富集分析指定宿主转录因子（SPI1）影响角膜炎的发病机制。分子对接分析发现，莪术醇-A 是一种有前途的细菌和宿主靶点抑制剂，其结合能范围从-7.59 到-6.20 kcal/mol。此外，MMGBSA 和 MD 模拟分析反映了莪术醇-A 与靶标之间更高的结合自由能和稳定的相互作用。此外，DFT 研究通过量子化学计算揭示了莪术醇-A 的化学反应性。因此，我们的研究结果表明莪术醇-A 是一种很有前途的有效抑制角膜炎的候选药物。然而，需要进一步的研究以将其潜在地整合到隐形眼镜护理解决方案中。
