Computational investigations of potential inhibitors of monkeypox virus envelope protein E8 through molecular docking and molecular dynamics simulations.
E8
MPXV
Maraviroc
Molecular docking
Molecular dynamics simulations
Punicalagin
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
received:
26
10
2023
accepted:
16
08
2024
medline:
24
8
2024
pubmed:
24
8
2024
entrez:
23
8
2024
Statut:
epublish
Résumé
The World Health Organization (WHO) has declared the monkeypox outbreak a public health emergency, as there is no specific therapeutics for monkeypox virus (MPXV) disease. This study focused on docking various commercial drugs and plant-derived compounds against the E8 envelope protein crucial for MPXV attachment and pathogenesis. The target protein structure was modeled based on the vaccinia virus D8L protein. Notably, maraviroc and punicalagin emerged as potential ligands, with punicalagin exhibiting higher binding affinity (- 9.1 kcal/mol) than maraviroc (- 7.8 kcal/mol). Validation through 100 ns molecular dynamics (MD) simulations demonstrated increased stability of the E8-punicalagin complex, with lower RMSD, RMSF, and Rg compared to maraviroc. Enhanced hydrogen bonding, lower solvent accessibility, and compact motions also attributed to higher binding affinity and stability of the complex. MM-PBSA calculations revealed van der Waals, electrostatic, and non-polar solvation as principal stabilizing energies. The binding energy decomposition per residue favored stable interactions between punicalagin and the protein's active site residues (Arg20, Phe56, Glu228, Tyr232) compared to maraviroc. Overall study suggests that punicalagin can act as a potent inhibitor against MPXV. Further research and experimental investigations are warranted to validate its efficacy and safety.
Identifiants
pubmed: 39179615
doi: 10.1038/s41598-024-70433-3
pii: 10.1038/s41598-024-70433-3
doi:
Substances chimiques
Viral Envelope Proteins
0
Maraviroc
MD6P741W8A
Antiviral Agents
0
Hydrolyzable Tannins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
19585Informations de copyright
© 2024. The Author(s).
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