Identification of Peptides as Novel Inhibitors to Target IFN-γ, IL-3, and TNF-α in Systemic Lupus Erythematosus

Autoimmune disorder is a chronic immune imbalance which is developed through a series of pathways. The defect in B cells, T cells, and lack of self-tolerance has been greatly associated with the onset of many types of autoimmune complications including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy. The SLE is an autoimmune disease with a common type of lupus that causes tissue and organ damage due to the wide spread of inflammation. In the current study, twenty anti-inflammatory peptides derived from plant and animal sources were docked as ligands or peptides counter to proinflammatory cytokines. Interferon gamma (IFN-gamma), interleukin 3 (IL-3), and tumor necrosis factor alpha (TNF-alpha) were targeted in this study as these are involved in the pathogenesis of SLE in many clinical studies. Two docking approaches (i.e., protein-ligand docking and peptide-protein docking) were employed in this study using Molecular Operating Environment (MOE) software and HADDOCK web server, respectively. Amongst docked twenty peptides, the peptide DEDTQAMMPFR with S-score of -11.3018 and HADDOCK score of -10.3 +/- 2.5 kcal/mol showed the best binding interactions and energy validation with active amino acids of IFN-gamma protein in both docking approaches. Depending upon these results, this peptide could be used as a potential drug candidate to target IFN-gamma, IL-3, and TNF-alpha proteins to control inflammatory events. Other peptides (i.e., QEPQESQQ and FRDEHKK) also revealed good binding affinity with IFN-gamma with S-scores of -10.98 and -10.55, respectively. Similarly, the peptides KHDRGDEF, FRDEHKK, and QEPQESQQ showed best binding interactions with IL-3 with S-scores of -8.81, -8.64, and -8.17, respectively.

Automated summary

Autoimmune disorder is a chronic immune imbalance caused by the defect in B cells, T cells, and lack of self-tolerance, which is closely related to the development of various autoimmune complications. In the current study, twenty anti-inflammatory peptides derived from plant and animal sources were investigated as potential ligands against proinflammatory cytokines.