Sinefungin analogs targeting VP39 methyltransferase as potential anti-monkeypox therapeutics: a multi-step computational approach.

Autor: Abouzied AS; Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, 81442, Hail, Saudi Arabia. as.ibrahim@uoh.edu.sa.; Medical and Diagnostic Research Center, University of Hail, 55473, Hail, Saudi Arabia. as.ibrahim@uoh.edu.sa., Huwaimel B; Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, 81442, Hail, Saudi Arabia.; Medical and Diagnostic Research Center, University of Hail, 55473, Hail, Saudi Arabia., Alqarni S; Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, 81442, Hail, Saudi Arabia., Younes KM; Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, 81442, Hail, Saudi Arabia.; Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt., Alshammari RE; College of Pharmacy, University of Hail, 81442, Hail, Saudi Arabia., Alshammari AH; College of Pharmacy, University of Hail, 81442, Hail, Saudi Arabia., Algharbi WF; College of Pharmacy, University of Hail, 81442, Hail, Saudi Arabia., Elkashlan AM; Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, El-Sadat, Egypt.
Jazyk: angličtina
Zdroj: Molecular diversity [Mol Divers] 2024 May 04. Date of Electronic Publication: 2024 May 04.
DOI: 10.1007/s11030-024-10875-z
Abstrakt: The increasing spread of the Monkeypox virus (MPXV) presents a significant public health challenge, emphasising the urgent requirement for effective treatments. Our study focuses on the VP39 Methyltransferase enzyme of MPXV as a critical target for therapy. By utilising virtual screening, we investigated natural compounds with structural similarities to sinefungin, a broad-acting MTase inhibitor. From an initial set of 177 compounds, we identified three promising compounds-CNP0346326, CNP0343532, and CNP008361, whose binding scores were notably close to that of sinefungin. These candidates bonded strongly to the VP39 enzyme, hinting at a notable potential to impede the virus. Our rigorous computational assays, including re-docking, extended molecular dynamics simulations, and energetics analyses, validate the robustness of these interactions. The data paint a promising picture of these natural compounds as front-runners in the ongoing race to develop MPXV therapeutics and set the stage for subsequent empirical trials to refine these discoveries into actionable medical interventions.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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