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.

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.

Antioxidants from different citrus peels provide protection against cancer.

Cancer is one of the leading causes of death. Despite significant advancements in the discovery of medications for the treatment of cancer, these drugs are hindered by applicability and efficacy issues and frequently exhibit major side effects that can further impair patients 'quality of life. Therefore, the development of therapeutically sound anti-cancer medicines derived from natural products has gained prominence in the field of functional foods. Some of these compounds have shown efficacy in the prevention and treatment of cancer as well as low toxicity. Additionally, many recent studies have explored the recycling of agro-industrial waste to create bioactive chemicals. Citrus peels are produced in vast quantities in the food processing sector; due to their abundance of flavonoids, they may be inexpensive sources of protection against several cancers. Citrus is a common type of fruit that contains a variety of nutrients. In particular, the antioxidant chemicals found in citrus peel have been identified as potential cancer-fighting agents. Antioxidant substances such as flavonoids prevent the development of cancer by inhibiting the metastatic cascade, decreasing the mobility of cancer cells in the circulatory system, promoting apoptosis, and suppressing angiogenesis. To explore the most effective uses of citrus peel-derived antioxidants, this review presents background information, an overview of the role of citrus antioxidants in cancer therapy, and a discussion of the key underlying molecular mechanisms.