Mycobacterium avium subspecies paratuberculosis (MAP) exhibits ‘molecular mimicry’ with the human host resulting in several autoimmune diseases such as multiple sclerosis, type 1 diabetes mellitus (T1DM), Hashimoto’s thyroiditis, Crohn’s disease (CD), etc. The conventional therapy for autoimmune diseases includes immunosuppressants or immunomodulators that treat the symptoms rather than the etiology and/or causative mechanism(s). Eliminating MAP–the etiopathological agent might be a better strategy to treat MAP-associated autoimmune diseases. In this case study, we conducted a systematic in silico analysis to identify the metabolic chokepoints of MAP’s mimicry proteins and their interacting partners. The probable inhibitors of chokepoint proteins were identified using DrugBank. DrugBank molecules were stringently screened and molecular interactions were analyzed by molecular docking and ‘off-target’ binding. Thus, we identified 18 metabolic chokepoints of MAP mimicry proteins and 13 DrugBank molecules that could inhibit three chokepoint proteins viz. katG, rpoB and narH. On the basis of molecular interaction between drug and target proteins finally eight DrugBank molecules, viz. DB00609, DB00951, DB00615, DB01220, DB08638, DB08226, DB08266 and DB07349 were selected and are proposed for treatment of three MAP-associated autoimmune diseases namely, T1DM, CD and multiple sclerosis. Because these molecules are either approved by the Food and Drug Administration or these are experimental drugs that can be easily incorporated in clinical studies or tested in vitro. The proposed strategy may be used to repurpose drugs to treat autoimmune diseases induced by other pathogens.

中文翻译：

---

识别治疗鸟分枝杆菌的新药物靶点。副结核病相关的自身免疫性疾病：一种计算机方法。

鸟分枝杆菌副结核亚种(MAP) 与人类宿主表现出“分子模拟”，导致多种自身免疫性疾病，如多发性硬化、1 型糖尿病 (T1DM)、桥本甲状腺炎、克罗恩病 (CD) 等。 自身免疫的常规疗法疾病包括治疗症状而非病因和/或致病机制的免疫抑制剂或免疫调节剂。消除 MAP——病原体可能是治疗 MAP 相关自身免疫性疾病的更好策略。在本案例研究中，我们进行了系统的计算机模拟分析以确定 MAP 模拟蛋白及其相互作用伙伴的代谢阻塞点。使用 DrugBank 鉴定了可能的阻塞点蛋白抑制剂。DrugBank 分子经过严格筛选，并通过分子对接和“脱靶”结合分析分子相互作用。因此，我们确定了 MAP 模拟蛋白的 18 个代谢阻塞点和可以抑制三种阻塞点蛋白的 13 个 DrugBank 分子。katG、rpoB 和 narH。基于药物和靶蛋白之间的分子相互作用，最终有八个 DrugBank 分子，即。选择 DB00609、DB00951、DB00615、DB01220、DB08638、DB08226、DB08266 和 DB07349，建议用于治疗三种 MAP 相关的自身免疫疾病，即 T1DM、CD 和多发性硬化症。因为这些分子要么已获得食品和药物管理局的批准，要么是可以轻松纳入临床研究或体外测试的实验药物。所提出的策略可用于重新利用药物来治疗由其他病原体引起的自身免疫性疾病。