In-silico Analysis of Potential Phytochemicals against VP39 Methyltransferase of Monkeypox virus
Keywords:
In-silico study, Monkeypox virus (MPXV)), VP39 Methyltransferase (MTase), molecular docking, Density functional theory (DFT)Abstract
Background: Monkeypox virus (MPXV), a zoonotic orthopoxvirus, has emerged as a global health concern, especially after the 2022 outbreak. Despite the rising prevalence, no drug has been specifically designed to treat MPXV. The VP39 methyltransferase (MTase) plays a vital role in mRNA capping, assisting the virus in immune evasion and replication, making it a promising antiviral target.
Objectives: This study aimed to identify natural phytochemical inhibitors against VP39 MTase of MPXV using computational drug discovery techniques, including molecular docking and density functional theory (DFT).
Methods: The crystal structure of VP39 MTase (PDB ID: 8cer) was obtained and validated using ERRAT, Verify3D, and PROCHECK. A total of 17,967 phytochemicals from the IMPPAT 2.0 database were screened based on ADMET properties and drug-likeness rules (Lipinski’s and Veber’s). Ninety-six compounds passed these filters and were docked using AutoDock Vina. The top ten ligands with the lowest binding energies were selected for further analysis, including interaction profiling and DFT evaluation to determine their chemical reactivity.
Results: The VP39 MTase structure was verified to be of high quality, with 93.5% of residues in the most favored regions. Among the 96 screened compounds, Hispidin (PubChem ID: 54685921) showed the lowest binding energy (-7.6 kcal/mol). Interaction analysis revealed multiple favorable interactions with active site residues. DFT analysis demonstrated a low HOMO-LUMO energy gap (ΔE = 0.12726 eV), suggesting high reactivity and potential as an effective inhibitor.
Conclusion: Hispidin emerged as a potent phytochemical candidate against VP39 MTase, showing strong binding affinity and favorable electronic properties. These findings provide a promising basis for further in vitro, in vivo, and molecular dynamics studies to develop novel anti-MPXV therapies
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