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Open AccessArticle

Using a Consensus Docking Approach to Predict Adverse Drug Reactions in Combination Drug Therapies for Gulf War Illness

1
Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA
2
Department of Psychology & Neuroscience, Nova Southeastern University, Fort Lauderdale, FL 33314, USA
3
Department of Clinical Immunology, Nova Southeastern University, Fort Lauderdale, FL 33314, USA
4
Pharmaceuticals and Bioengineering Department, Southwest Research Institute, San Antonio, TX 78238, USA
5
Pharmaceuticals and Bioengineering, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX 78238, USA
6
Miami Veterans Affairs Medical Center, Miami, FL 33125, USA
7
Centre for Clinical Systems Biology, Rochester General Hospital Research Institute, Rochester, NY 14617, USA
8
Rochester Institute of Technology, Rochester, NY 14623, USA
9
Department of Computer Science, Nova Southeastern University, Fort Lauderdale, FL 33314, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3355; https://doi.org/10.3390/ijms19113355
Received: 22 August 2018 / Revised: 1 October 2018 / Accepted: 16 October 2018 / Published: 26 October 2018
Gulf War Illness (GWI) is a chronic multisymptom illness characterized by fatigue, musculoskeletal pain, and gastrointestinal and cognitive dysfunction believed to stem from chemical exposures during the 1990–1991 Persian Gulf War. There are currently no treatments; however, previous studies have predicted a putative multi-intervention treatment composed of inhibiting Th1 immune cytokines followed by inhibition of the glucocorticoid receptor (GCR) to treat GWI. These predictions suggest the use of specific monoclonal antibodies or suramin to target interleukin-2 and tumor necrosis factor α , followed by mifepristone to inhibit the GCR. In addition to this putative treatment strategy, there exist a variety of medications that target GWI symptomatology. As pharmaceuticals are promiscuous molecules, binding to multiple sites beyond their intended targets, leading to off-target interactions, it is key to ensure that none of these medications interfere with the proposed treatment avenue. Here, we used the drug docking programs AutoDock 4.2, AutoDock Vina, and Schrödinger’s Glide to assess the potential off-target immune and hormone interactions of 43 FDA-approved drugs commonly used to treat GWI symptoms in order to determine their putative polypharmacology and minimize adverse drug effects in a combined pharmaceutical treatment. Several of these FDA-approved drugs were predicted to be novel binders of immune and hormonal targets, suggesting caution for their use in the proposed GWI treatment strategy symptoms. View Full-Text
Keywords: Gulf War Illness; consensus docking; off-target interactions; side effects; multi-drug therapy; polypharmacology; treatment course design Gulf War Illness; consensus docking; off-target interactions; side effects; multi-drug therapy; polypharmacology; treatment course design
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Jaundoo, R.; Bohmann, J.; Gutierrez, G.E.; Klimas, N.; Broderick, G.; Craddock, T.J.A. Using a Consensus Docking Approach to Predict Adverse Drug Reactions in Combination Drug Therapies for Gulf War Illness. Int. J. Mol. Sci. 2018, 19, 3355.

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