Contact lens-mediated microbial keratitis caused by Pseudomonas aeruginosa and Streptococcus pneumoniae provokes corneal damage and vision loss. Recently, natural phytochemicals have become complementary medicines for corneal destruction. Herein, we aimed to identify multi-targeting Aloe vera-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.

中文翻译：

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芦荟树脂 A 对细菌和宿主炎症靶标的多靶点作用有益于隐形眼镜相关角膜炎：多组学和量子化学研究

由铜绿假单胞菌和肺炎链球菌引起的隐形眼镜介导的微生物性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角膜破坏的补充药物。在此，我们的目的是通过ADME（吸收、分布、代谢和排泄）、对接、分子动力学（MD）模拟、MMGBSA（广义分子力学）来鉴定能够抑制角膜炎细菌和宿主靶点的多靶点芦荟植物化学物质。玻恩表面积）和密度泛函理论（DFT）研究。广泛的文献检索显示 ExoU、ExoS、ExoT、ExoY 和 PLY 是有毒细菌靶标。同时，差异基因表达（DGE）和通路富集分析特定宿主转录因子（SPI1）影响角膜炎的发病机制。分子对接分析发现芦荟素-A 是一种很有前景的细菌和宿主靶标抑制剂，其结合能范围为 -7.59 至 -6.20 kcal/mol。此外，MMGBSA 和 MD 模拟分析反映了芦荟树脂-A 与靶标的较高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芦荟树脂-A 的化学反应性。因此，我们的研究结果表明芦荟树脂-A 是有效抑制角膜炎的有希望的候选者。然而，为了将其整合到镜片护理解决方案中，还需要进行更多的研究。