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المؤلفSuleman, Muhammad
المؤلفAhmad, Tanveer
المؤلفshah, Khadim
المؤلفAlbekairi, Norah A.
المؤلفAlshammari, Abdulrahman
المؤلفKhan, Abbas
المؤلفWei, Dong-Qing
المؤلفYassine, Hadi M.
المؤلفCrovella, Sergio
تاريخ الإتاحة2024-04-24T09:53:24Z
تاريخ النشر2023
اسم المنشورFrontiers in Pharmacology
المصدرScopus
الرقم المعياري الدولي للكتاب16639812
معرّف المصادر الموحدhttp://dx.doi.org/10.3389/fphar.2023.1328308
معرّف المصادر الموحدhttp://hdl.handle.net/10576/54212
الملخصAmid the ongoing monkeypox outbreak, there is an urgent need for the rapid development of effective therapeutic interventions capable of countering the immune evasion mechanisms employed by the monkeypox virus (MPXV). The evasion strategy involves the binding of the F3L protein to dsRNA, resulting in diminished interferon (IFN) production. Consequently, our current research focuses on utilizing virtual drug screening techniques to target the RNA binding domain of the F3L protein. Out of the 954 compounds within the South African natural compound database, only four demonstrated notable docking scores: -6.55, -6.47, -6.37, and -6.35 kcal/mol. The dissociation constant (KD) analysis revealed a stronger binding affinity of the top hits 1-4 (-5.34, -5.32, -5.29, and -5.36 kcal/mol) with the F3L in the MPXV. All-atom simulations of the top-ranked hits 1 to 4 consistently exhibited stable dynamics, suggesting their potential to interact effectively with interface residues. This was further substantiated through analyses of parameters such as radius of gyration (Rg), Root Mean Square Fluctuation, and hydrogen bonding. Cumulative assessments of binding free energy confirmed the top-performing candidates among all the compounds, with values of -35.90, -52.74, -28.17, and -32.11 kcal/mol for top hits 1-4, respectively. These results indicate that compounds top hit 1-4 could hold significant promise for advancing innovative drug therapies, suggesting their suitability for both in vivo and in vitro experiments. Copyright
راعي المشروعThe author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Qatar University Grant No. QUPD-CAS-23-24-491.
اللغةen
الناشرFrontiers Media SA
الموضوعbinding free energy
drug screening
dsRNA
MD simulation
monkeypox
العنوانExploring the natural products chemical space to abrogate the F3L-dsRNA interface of monkeypox virus to enhance the immune responses using molecular screening and free energy calculations
النوعArticle
رقم المجلد14
dc.accessType Open Access


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