In Silico Identification of Promising IL-6 Inhibitors Among Natural Derivatives: A Docking, MM-GBSA and ADMET Study

Abstract

Interleukin-6 (IL-6) is recognized as a B cell stimulation factor that promotes the transformation of effector B cells into antibody-producing cells. The association between the disruption of IL-6 signalling and the onset of several illnesses, such as psoriasis, has been established. Presently, therapeutic agents that suppress IL-6, such as siltuximab, have been identified and are used to manage several persistent inflammatory disorders. Notwithstanding the well-documented advantages linked to monoclonal antibody treatment, it is crucial to recognize that these biological agents also exhibit significant limitations, such as their high prices. Objectives: The objective of this study was the identification of natural derivatives that exhibit strong binding affinity against IL-6. Methods: In order to achieve the objective, docking, MMGBSA, and ADMET investigations were conducted. Molecular docking was performed on the library of natural derivatives using Schrodinger's Glide tool, explicitly targeting IL-6. The Prime-MMGBSA approach was used to determine the binding free energy of selected natural derivatives. In-silico ADMET profiling was performed using the pkCSM web server. Results: Several natural derivatives had exceptional docking scores, suggesting their potential to serve as anti-IL-6 agents. Our result indicated Shikimic acid, Indole-3-butyric acid, and Tubericidin exhibited docking scores below -5.2. Additionally, these compounds exhibited exceptional drug-like features. Conclusions: This work identifies the possible inhibitory effects of several natural derivatives on IL-6. Shikimic acid, Indole-3-butyric acid and Tubericidin have a high binding affinity and favourable ADMET profile, thus making them potential potent inhibitors of IL-6. However, further in-vitro and in-vivo study is required.