AI-driven Discovery of Celecoxib and Dexamethasone for Exploring their Mode of Action as Human Interleukin (IL-6) Inhibitors to Treat COVID-19-induced Cytokine Storm in Humans

• DOI: 10.2174/0113816128260449231017091824
• Publication Date: 2023-11-06T07:33:33Z
• Authors: Israa M. Shamkh; Mahmoud Elkazzaz; Enas. S. Radwan; Jawayria Najeeb; Md. Tabish Rehman; Mohamed F. AlAjmi; Moayad Shahwan; Muhammad Sufyan; Nouf Khalifa Alaqeel; Ibrahim A. Ibrahim; Basit Jabbar; Mohammad Shahbaz ...; Tomasz M. Karpiński; Abdullah Haikal; Reem M. Aljowaie; Saeedah Musaed Al...; Amr Ahmed
• Keywords: Cytokine Storm; Docking (animal); Mode of Action

Background:: In the case of COVID-19 patients, it has been observed that immune system infected person exhibits an extreme inflammatory response known as cytokine release syndrome (CRS) where cytokines are swiftly produced in quite large amounts to infective stimuli. Numerous studies patients with severe symptoms have documented presence higher plasma concentrations human interleukin-6 (IL-6), which suggests IL-6 is a crucial factor pathophysiology disease. order prevent CRS drugs can exhibit binding interactions and block signaling pathways decrease activity may be repurposed. Methods:: This research work focused on molecular docking-based screening celecoxib (CXB) dexamethasone (DME) explore their potential interact sites protein reduce hyper-activation personnel. Results:: Both were bind (IL-6 receptor alpha chain) IL-6Rα respective affinities -7.3 kcal/mol -6.3 kcal/mol, respectively, for CXB DME. Moreover, various types target proteins also docking studies. The dynamic behaviors IL-6/IL-6Rα complex explored through dynamics simulation analysis. results indicated significant stabilities acquired drug-protein complexes up 100 ns. Conclusion:: findings this study suggested studied utilized antagonists countering ailment. presents promising candidates both clinical pre-clinical treatment COVID-19.