Jaundoo Rajeev, Bohmann Jonathan, Gutierrez Gloria E, Klimas Nancy, Broderick Gordon, Craddock Travis J A
Institute for Neuro-Immune Medicine, Nova Southeastern University, 3301 College Avenue, Fort Lauderdale, FL 33314-7796.
Department of Psychology & Neuroscience, Nova Southeastern University, 3301 College Avenue, Fort Lauderdale, FL 33314-7796.
Mil Med. 2020 Jan 7;185(Suppl 1):554-561. doi: 10.1093/milmed/usz299.
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.
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.
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.
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.
海湾战争疾病（GWI）目前尚无已知的治愈方法，影响在海湾战争期间部署的士兵。人们认为它源于接触神经毒物并伴有战场压力，先前的研究表明，治疗首先涉及抑制白细胞介素-2和肿瘤坏死因子α，随后是糖皮质激素受体。然而，药物的脱靶效应阻碍了药物治疗方法的发展。
使用AutoDock 4.2、AutoDock Vina和薛定谔的Glide进行一致性对接，这是一种计算技术，通过使用多种评分算法针对靶点筛选药物以获得一致的结合亲和力。将美国食品药品监督管理局（FDA）批准的药物与上述免疫和应激靶点进行对接，以确定针对GWI的药物治疗方法。此外，还对雄激素和雌激素靶点进行了筛选，以避免具有脱靶相互作用的药物。
虽然苏拉明以高亲和力与两个免疫靶点结合，但激素和糖皮质激素靶点的顶级结合物对各自的蛋白质不具有特异性，这可能是由于这些蛋白质之间的高度结构相似性。
免疫和激素系统之间的紧密相互作用常常导致药物相互作用，这威胁到GWI药物治疗方法的开发。对这些相互作用的了解不断增加可能会带来突破性疗法。
