INTRODUCTION:Gulf War Illness (GWI) currently has no known cure and affects soldiers deployed during the Persian Gulf War. It is thought to originate from exposure to neurotoxicants combined with battlefield stress, and previous research indicates that treatment first involves inhibition of interleukin-2 and tumor necrosis factor alpha, followed by the glucocorticoid receptor. However, the off-target effects of pharmaceuticals hinder development of a drug treatment therapy. MATERIALS AND METHODS:AutoDock 4.2, AutoDock Vina, and Schrodinger's Glide were used to perform consensus docking, a computational technique where pharmaceuticals are screened against targets using multiple scoring algorithms to obtain consistent binding affinities. FDA approved pharmaceuticals were docked against the above-mentioned immune and stress targets to determine a drug therapy for GWI. Additionally, the androgen and estrogen targets were screened to avoid pharmaceuticals with off-target interactions. RESULTS:While suramin bound to both immune targets with high affinity, top binders of the hormonal and glucocorticoid targets were non-specific towards their respective proteins, possibly due to high structure similarity between these proteins. CONCLUSIONS:Development of a drug treatment therapy for GWI is threatened by the tight interplay between the immune and hormonal systems, often leading to drug interactions. Increasing knowledge of these interactions can lead to break-through therapies.

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简介:海湾战争疾病(GWI)目前尚无治愈方法,会影响在波斯湾战争期间部署的士兵。据认为,这是由于暴露于神经毒物并伴随战场压力而引起的,以前的研究表明,治疗首先涉及抑制白介素2和肿瘤坏死因子α,然后抑制糖皮质激素受体。然而,药物的脱靶效应阻碍了药物治疗疗法的发展。
材料与方法:使用AutoDock 4.2,AutoDock Vina和Schrodinger's Glide进行共识对接,这是一种计算技术,其中使用多种评分算法针对目标筛选药物以获得一致的结合亲和力。 FDA批准的药物与上述免疫和应激目标对接,以确定GWI的药物疗法。另外,筛选雄激素和雌激素靶标,以避免药物与靶标之间发生相互作用。
结果:虽然苏拉明以高亲和力结合到两个免疫靶标上,但激素和糖皮质激素靶标的主要结合剂对其各自的蛋白质没有特异性,这可能是由于这些蛋白质之间的高度结构相似性所致。
结论:免疫和激素系统之间的紧密相互作用威胁着GWI药物治疗疗法的发展,常常导致药物相互作用。对这些相互作用的了解不断增加,可能会带来突破性的疗法。

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