Ravi Lokesh, Kumar K Ajith, G R Shree Kumari, Mathew Jesna, S Harshitha, Panda Mukti, S Shivani, Paul Ayona, Ts Chandana, Anil Aswani, J K Megha, Mukherjee Taanusiya, Bhattacharjee Sneha, Raveendran Nair Manu, V Subhanjan, V Mohanasrinivasan, Jain Pratishtha
Department of Food Technology, Faculty of Life and Allied Health Sciences, MS Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India.
Department of Life Sciences, Kristu Jayanti College (Autonomous), Bengaluru, Karnataka, India.
J Biomol Struct Dyn. 2024 Feb 14:1-16. doi: 10.1080/07391102.2024.2317988.
Multi-Target Inhibitors are the upcoming frontrunners of the antibiotic world as they provide significant advantage over drug resistance development. Antibacterial drug discovery research, requires more robust and innovative approaches such as multi-target inhibiting drugs, which over comes the innate hurdles in the field of antibiotics. In this current study, a curated set of 5,112 phytochemical molecules were virtually screened for its multi-target inhibition potential against 7 antibacterial protein drug-targets. Behenic Acid was identified to be the most significant phytochemical molecule with potential to inhibit Catalase Peroxidase (KatG), Adenylosuccinate Synthetase (ADSS) and Pyridoxine 5'-Phosphate Synthase (PdxJ), based on SeeSAR and AutoDock Vina results. Further, the inhibition potential of Behenic Acid was validated using 500 ns Molecular Dynamics (MD) Simulation based on Desmond analysis. Behenic Acid was further investigated in-vitro using agar-well-diffusion and Minimal Inhibitory Concentration (MIC) assay, where it demonstrated 20 ± 1mm zone-of-inhibition and 50 µg/ml MIC value against both and . Zebrafish based investigations was carried to confirm the in-vivo antibacterial efficacy of Behenic Acid. It was observed that, there is a progressive dose-dependent recovery from the bacterial infection, with highest recovery and survival observed in fishes fed with 100 µg/day of Behenic Acid. Results of the in-vitro and in-vivo assays strongly support the in-silico prediction of the antibacterial activity of Behenic Acid. Based on the results presented in this study, it is concluded that, Behenic Acid is a strong multi-target antibacterial phytochemical, that exerts antagonism against aquaculture bacterial pathogens such as and
多靶点抑制剂是抗生素领域即将崛起的领先者，因为它们在抗耐药性发展方面具有显著优势。抗菌药物发现研究需要更强大和创新的方法，如多靶点抑制药物，这克服了抗生素领域的固有障碍。在本研究中，对一组精心挑选的5112种植物化学分子进行了虚拟筛选，以评估其对7种抗菌蛋白药物靶点的多靶点抑制潜力。根据SeeSAR和AutoDock Vina的结果，山嵛酸被确定为最具潜力的植物化学分子，它有可能抑制过氧化氢酶过氧化物酶（KatG）、腺苷琥珀酸合成酶（ADSS）和磷酸吡哆醛5'-磷酸合成酶（PdxJ）。此外，基于Desmond分析，通过500纳秒的分子动力学（MD）模拟验证了山嵛酸的抑制潜力。使用琼脂孔扩散法和最低抑菌浓度（MIC）测定法对山嵛酸进行了进一步的体外研究，结果表明它对[具体细菌1]和[具体细菌2]的抑菌圈直径为20±1毫米，MIC值为50微克/毫升。进行了基于斑马鱼的研究以确认山嵛酸的体内抗菌效果。观察到，从细菌感染中恢复呈现出剂量依赖性的进展，喂食100微克/天山嵛酸的鱼类恢复率和存活率最高。体外和体内试验的结果有力地支持了山嵛酸抗菌活性的计算机模拟预测。基于本研究的结果，得出结论：山嵛酸是一种强大且具有多靶点抗菌活性的植物化学物质，对[具体细菌1]和[具体细菌2]等水产养殖病原菌具有拮抗作用。
