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AuthorSuleman, Muhammad
AuthorAhmad, Tanveer
Authorshah, Khadim
AuthorAlbekairi, Norah A.
AuthorAlshammari, Abdulrahman
AuthorKhan, Abbas
AuthorWei, Dong-Qing
AuthorYassine, Hadi M.
AuthorCrovella, Sergio
Available date2024-04-24T09:53:24Z
Publication Date2023
Publication NameFrontiers in Pharmacology
ResourceScopus
ISSN16639812
URIhttp://dx.doi.org/10.3389/fphar.2023.1328308
URIhttp://hdl.handle.net/10576/54212
AbstractAmid 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
SponsorThe 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.
Languageen
PublisherFrontiers Media SA
Subjectbinding free energy
drug screening
dsRNA
MD simulation
monkeypox
TitleExploring 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
TypeArticle
Volume Number14
dc.accessType Open Access


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