Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, China.
School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, China.
Chem Biol Drug Des. 2023 Dec;102(6):1353-1366. doi: 10.1111/cbdd.14322. Epub 2023 Aug 20.
Calcium channel blocker (CCB) is known to possess antibacterial effects. We aimed to apply network pharmacology (docking and protein-protein interaction [PPI] analyses) to predict the potential targets and mechanisms of CCB against Pseudomonas aeruginosa (PA) as well as to verify the effect of these drugs. The chemical structures of three CCBs were obtained through the Drug Bank platform. The potential channel proteins, efflux pump proteins and ion channel proteins of CCB against bacteria were derived from the literature. These proteins were collected through the PDB and Uniprot platform. The binding mode of the docking complexes was simulated by the CB-Dock platform and Discovery Studio 2019 Client software. The PPI network was constructed by the String platform and Cytoscape 3.8.2 platform. GO was explained by the PANTHER platform. The pathway diagram was drawn with the Pathway Builder Tool 2.0 software. The inhibitory effect of CCB on PA was verified through antibacterial experiments. Finally, 76 proteins were obtained: the iron channel protein of PA demonstrated a good docking relationship with all three CCBs, and the optimum binding energy was approximately -9.0 kcal/mol. GO analysis (biological process [BP], cellular component [CC], and molecular function [MF]) of protein genes showed a good docking relationship (optimum binding energy <-8.0 kcal/mol). The MF annotation results indicated that the target of CCB may be present on the PA membrane protein. The ion channel protein PPI enrichment p-value was 6.65e-08, and PfeA showed the strongest correlation. The experimental results suggested that CCB could inhibit the growth of PA. CCB might be an effective and interesting antimicrobial treatment strategy as CCB can potentially inhibit the growth of PA.
钙通道阻滞剂（CCB）具有抗菌作用。本研究旨在应用网络药理学（对接和蛋白质-蛋白质相互作用[PPI]分析）预测 CCB 对铜绿假单胞菌（PA）的潜在靶点和作用机制，并验证这些药物的效果。通过 Drug Bank 平台获取三种 CCB 的化学结构。从文献中获取 CCB 对细菌的潜在通道蛋白、外排泵蛋白和离子通道蛋白。通过 PDB 和 Uniprot 平台收集这些蛋白质。使用 CB-Dock 平台和 Discovery Studio 2019 Client 软件模拟对接复合物的结合模式。通过 String 平台和 Cytoscape 3.8.2 平台构建 PPI 网络。使用 PANTHER 平台解释 GO。使用 Pathway Builder Tool 2.0 软件绘制通路图。通过抗菌实验验证 CCB 对 PA 的抑制作用。最终得到 76 种蛋白：PA 的铁通道蛋白与三种 CCB 均表现出良好的对接关系，最佳结合能约为-9.0 kcal/mol。GO 分析（生物过程[BP]、细胞成分[CC]和分子功能[MF]）显示蛋白基因具有良好的对接关系（最佳结合能<-8.0 kcal/mol）。MF 注释结果表明，CCB 的靶点可能存在于 PA 膜蛋白上。离子通道蛋白 PPI 富集的 p 值为 6.65e-08，其中 PfeA 相关性最强。实验结果表明 CCB 可以抑制 PA 的生长。CCB 可能是一种有效且有趣的抗菌治疗策略，因为 CCB 可能潜在地抑制 PA 的生长。
