Towards a Treatment for Gulf War Illness: A Consensus Docking Approach (2020) Jaundoo et al

Towards a Treatment for Gulf War Illness: A Consensus Docking Approach

Rajeev Jaundoo, BSc, Jonathan Bohmann, PhD, Gloria E Gutierrez, PhD, Nancy Klimas, MD, Gordon Broderick, PhD, Travis J A Craddock, PhD

Full text here
(note: When i post papers pertaining to GWI I always wonder whether i should put it in ME research papers category because the diseases are closely related, and also because often times the researchers in GWI also study ME, but then the research unrelated to ME is not the correct category either)

Abstract

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

 

Nancy Klimas talks a bit about this research (makes it sound a lot more interesting than this paper) and how they plan to apply it to ME/CFS in a podcast here

https://www.s4me.info/threads/post-...fs-2019-klimas-et-al.12900/page-3#post-273873

(I think I picked the wrong thread to post the podcast in)