Structural modulation of dual oxidase (Duox) in Drosophila melanogaster by phyto-elicitors: A free energy study with molecular dynamics approach

Abstract

The gut, as a paradigm is considered to be the second brain, plays a pivotal role in maintaining a healthy metabolism and negatively modulates dysbiosis at both the micro and macro levels. The gut-immune barrier is responsible for regulating major immune centers from inflammation, T-cell subsets (Th1, Th2, Th17, Tregs), chemotaxis, and chemokinesis to death. Oxidative stress is established as a prime reason for leaky gut disorders. Further, the Dual oxidase (Duox) pathway plays a major role in oxidant generation during a bacterial-metabolite attack in the host. The current study attempts to explore the possibilities of repurposing phytobioactives from the banana plant (Musa sp. var. Nanjangud Rasa Bale) as Duox inhibitors using Drosophila melanogaster as a model system for human biomimics. As a result of our previous studies, well-established antidiabetic ligands were implicated in treating diabetic neuropathy in the fly model. Complexes of Duox-STI, Duox-BST, Duox-LUP, and Duox-UMB were subjected to molecular docking, simulation with Duox-Captopril (CAP) as a standard drug reference. The result elucidates the inhibitory potency of phyto-ligands with their intermolecular interactions. UMB was found to be very much promising as an inhibitor on the Dual oxidase enzyme. This study corroborates the findings on the immune deficiency (Imd) pathway by providing evidence of the effectiveness of phytobioactives. Further, the inference of the study emphasizes to consider Drosophila as a therapeutic research model to probe gut-related disease including microbiome research to ameliorate immunity, diabetes, and diabetic neuropathy, or any lifestyle metabolic disorders which could lead to the design and development of smarter herbaceuticals.

Keywords

• Duox
• Imd
• Oxidants
• Antimicrobial peptides
• Inflammation
• Microbiome