Towards a Treatment for Gulf War Illness: A Consensus Docking Approach.
Journal
Military medicine
ISSN: 1930-613X
Titre abrégé: Mil Med
Pays: England
ID NLM: 2984771R
Informations de publication
Date de publication:
07 01 2020
07 01 2020
Historique:
received:
07
02
2019
revised:
02
08
2019
accepted:
02
08
2019
entrez:
20
2
2020
pubmed:
20
2
2020
medline:
15
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32074351
pii: 5740749
doi: 10.1093/milmed/usz299
pmc: PMC7029833
doi:
Substances chimiques
Lymphokines
0
Tumor Necrosis Factor Inhibitors
0
interleukin 2 inhibitor
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
554-561Informations de copyright
© Oxford University Press 2020.
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