Page 104 - Pharma News Letter - Vol2 Issue 1

Chapter V

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

Current Pharmaceutical Design. 2023 Oct; 29(34): 2752 – 2762.

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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

Khan, Tomasz M. Karpiński, Abdullah Haikal, Reem M. Aljowaie, Saeedah

Abstract Musaed Almutairi, Amr Ahmed

Background: In the case of COVID-19 patients, it has been observed that the immune system
of the infected person exhibits an extreme inflammatory response known as cytokine release
syndrome (CRS) where the inflammatory cytokines are swiftly produced in quite large amounts
in response to infective stimuli. Numerous case studies of COVID-19 patients with severe
symptoms have documented the presence of higher plasma concentrations of human interleukin-6
(IL-6), which suggests that IL-6 is a crucial factor in the pathophysiology of the disease. In order
to prevent CRS in COVID-19 patients, the drugs that can exhibit binding interactions with IL-6
and block the signaling pathways to decrease the IL-6 activity may be repurposed.

Methods: This research work focused on molecular docking-based screening of the drugs
celecoxib (CXB) and dexamethasone (DME) to explore their potential to interact with the
binding sites of IL-6 protein and reduce the hyper-activation of IL-6 in the infected personnel.

Results: Both of the drugs were observed to bind with the IL-6 (IL-6 receptor alpha chain) and
IL-6Rα receptor with the respective affinities of -7.3 kcal/mol and -6.3 kcal/mol, respectively,
for CXB and DME. Moreover, various types of binding interactions of the drugs with the target
proteins were also observed in the docking studies. The dynamic behaviors of IL-6/IL-6Rα in
complex with the drugs were also explored through molecular dynamics simulation analysis.
The results indicated significant stabilities of the acquired drug-protein complexes up to 100 ns.

Conclusion: The findings of this study have suggested the potential of the drugs studied to be
utilized as antagonists for countering CRS in COVID-19 ailment. This study presents the studied
drugs as promising candidates both for the clinical and pre-clinical treatment of COVID-19.

Reference:

https://doi.org/10.2174/0113816128260449231017091824

104 Faculty of Pharmacy Newsletter