Structure-Based Discovery of Bioactive Bisindole and Aporphine Alkaloids from Traditional Chinese Medicine as Novel Natural IL-17 and MRSA Inhibitors

This dataset contains all structural files, docking inputs/outputs, and supporting analytical data used in the virtual screening, refined docking, and NMR characterization of isolated alkaloids investigated in this study. The files provided enable full reproducibility of computational workflows and structural analyses as required by JCIM. Omar M. Khattab a, Nermeen Yosri b, Qianqian Liu a, Zhuoda Zhou a, Jianxin Han a, Zhixin Ling a, Jiang Sun a, Yajie Wang a, Mohamed A. Farag c, Huiying Fu d*, and Qiyang Shou a,d* a Jinhua Academy of Zhejiang Chinese Medical University, Jinhua 321000, China b China Light Industry Key Laboratory of Food Intelligent Detection & Processing, School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China c Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, 11562, Cairo, Egypt d The Second Affiliated Hospital & Second Clinical Medical School, Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou 310053, China Traditional Chinese medicine (TCM) represents an untapped reservoir of bioactive alkaloids with immense pharmacological potential. This study integrates computational screening with bioassay-guided isolation to uncover strychnochrysine and aporphine alkaloids from Strychnos nux-vomica and Aristolochia contorta as promising dual-acting agents against Methicillin-Resistant Staphylococcus aureus (MRSA) and IL-17-mediated inflammatory responses. A virtual library of 983 alkaloids derived from 82 TCM species was screened through multi-target molecular docking against bacterial resistance enzymes and the IL-17 receptor, revealing 50 high-affinity ligands (binding energies ≤ -7 kcal/mol). Molecular dynamics simulations confirmed the stability of alkaloid-protein complexes, particularly for bisindole strychnines. Guided by in-silico results, bioassay isolation yielded 24 active alkaloids with MIC50 values of 0.3-1 mg/mL against S. aureus bacteria. The study not only identifies new immunomodulatory and antibacterial leads but also establishes a computational experimental workflow for accelerating natural product drug discovery. Overall, this study provides a comprehensive database of alkaloids isolated from TCM, which can serve as potential candidates for IL-17 inhibition associated with MRSA infections, highlighting TCM alkaloids as potent scaffolds for next-generation anti-MRSA therapeutics and as model compounds bridging ethnomedicine with modern chemical biology.