Biotechnology Program, School of Bioresources and Technology (SBT), King Mongkut's University of Technology Thonburi (KMUTT), Bang Khun Thian, Bangkok, Thailand.
Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand.
PLoS One. 2024 Aug 29;19(8):e0309303. doi: 10.1371/journal.pone.0309303. eCollection 2024.
Immunosuppressive drugs are essential for systemic lupus erythematosus (SLE) treatment, but there are concerns about their toxicity. In this study, Arthrospira platensis was used as a resource for screening of the SLE-related bioactive compounds. To discover the potential compounds, a total of 833 compounds of A. platensis C1 were retrieved from the Spirulina-Proteome Repository (SpirPro) database and by literature mining. We retrieved structures and bioassays of these compounds from PubChem database; and collected approved and potential drugs for SLE treatment from DrugBank and other databases. The result demonstrated that cytidine, desthiobiotin, agmatine, and anthranilic acid, from the alga, has Tanimoto matching scores of 100% with the following drugs: β-arabinosylcytosine/cytarabine, d-dethiobiotin, agmatine, and anthranilic acid, respectively. The bioassay matching and disease-gene-drug-compound network analysis, using VisANT 4.0 and Cytoscape, revealed 471 SLE-related genes. Among the SLE-related genes, MDM2, TP53, and JAK2 were identified as targets of cytarabine, while PPARG and IL1B were identified as targets of d-dethiobiotin. Binding affinity between the drug ligands and the algal bioactive compound ligands with their corresponding receptors were similarly comparable scores and stable, examined by molecular docking and molecular dynamic simulations, respectively.
免疫抑制剂是治疗系统性红斑狼疮（SLE）的重要药物，但人们对其毒性存在担忧。在这项研究中，我们将螺旋藻作为筛选与 SLE 相关的生物活性化合物的资源。为了发现潜在的化合物，我们从螺旋藻蛋白质组资源库（SpirPro）数据库和文献挖掘中检索了 833 种螺旋藻 C1 化合物。我们从 PubChem 数据库中检索了这些化合物的结构和生物测定结果；并从 DrugBank 和其他数据库中收集了用于治疗 SLE 的已批准和潜在药物。结果表明，来自藻类的胞苷、去硫生物素、胍丁胺和邻氨基苯甲酸与以下药物具有 100%的 Tanimoto 匹配得分：β-阿拉伯呋喃糖基胞苷/阿糖胞苷、去硫生物素、胍丁胺和邻氨基苯甲酸。使用 VisANT 4.0 和 Cytoscape 进行的生物测定匹配和疾病-基因-药物-化合物网络分析揭示了 471 个与 SLE 相关的基因。在与 SLE 相关的基因中，鉴定出阿糖胞苷的靶标为 MDM2、TP53 和 JAK2，而 d-去硫生物素的靶标为 PPARG 和 IL1B。通过分子对接和分子动力学模拟分别检查了药物配体和藻类生物活性化合物配体与相应受体之间的结合亲和力，结果表明它们的得分和稳定性相似。
