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Structure-based Virtual Screening of Natural Compounds as Potential Anti-Allergy Agents Against Cytokine Alarmins (TSLP and IL-33)

[ Vol. 18 , Issue. 9 ]


Rahma Muhammad Adamu, Rita Singh Majumdhar and Abdullahi Ibrahim Uba*   Pages 932 - 942 ( 11 )


<p>Background: Allergic diseases are turning into an expanding occurrence around the globe, imposing a socioeconomic burden, causing grimness and even death. Allergen encounter initiates the influx of TH2 cells, triggering the production of T<sub>H</sub>2 associated cytokines (IL-4, IL-5, and IL-13), which in turn promotes the detrimental allergic inflammation associated with asthma, allergic rhinitis, food allergy, urticaria, atopic eczema, and anaphylaxis. Cytokine alarmins (TSLP and IL-33) produced by epithelial cells play important roles in the promotion of T<sub>H</sub>2 cell development and the initiation of allergic pathogenesis. </P><P> Objective: To target cytokine alarmins (TSLP and IL-33) as novel therapeutic proteins, using natural compounds as a potential cure at an early stage of allergic diseases. </P><P> Methods: Structure-based virtual screening of two large natural compounds databases (Universal Natural product Database (UNPD) and ZINC natural product database) was conducted for the identification of TSLP and IL-33 inhibitors using Autodock Vina followed by rescoring of the hit compounds. using Autodock 4.2 software. In silico physicochemical, pharmacokinetic, and toxicity analyses were conducted to assess the drug-like properties of the hit compounds. The binding mode stability of UNPD116849, ZINC01448143, and ZINC04096134 in the binding pocket of TSLP and IL-33 was probed by all-atom 50 ns molecular dynamics simulation. </P><P> Results: Five natural compounds (UNPD111, UNPD116849, ZINC01448143, ZINC15957528, and ZINC04096134) containing different structural moieties (steroidal, chromone, benzodioxole, and indole) were identified to inhibit TSLP and IL-33, with limonin (ZINC04096134) found to demonstrate dual inhibitory activity potential. These compounds were found to be drug-like and toxicity-free using in silico Absorption, Distribution, Metabolism, Elimination, and Toxicity (ADME-T) prediction methods. Taken together, this study suggests the dual inhibition potential of limonin (ZINC04096134) against the cytokine alarmins. </P><P> Conclusion: Five natural compounds with diverse structural moieties (steroidal, chromone, benzodioxole, and indole) were virtually identified as hit compounds against cytokine alarmins (TSLP and IL-33), with limonin showing dual inhibitory potential.</p>


Allergic diseases, natural compounds, T<sub>H</sub>2 cytokines, structure-based virtual screening, TSLP and IL-33.


Department of Biotechnology, School of Engineering and Technology, Sharda University, New Delhi, Department of Biotechnology, School of Engineering and Technology, Sharda University, New Delhi, Complex Systems Division, Beijing Computational Science Research Center, Beijing 100193

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