In Silico Characterization and Structural Validation of VP39 Methyltransferase as a Potential Antiviral Target against Monkeypox Virus
Keywords:
Antiviral agents, Methyltransferase, Molecular docking, Monkeypox virus, Protein structure, SimulationAbstract
Background: Monkeypox virus (MPXV) is a zoonotic double-stranded DNA virus of the Poxviridae family. With increasing global outbreaks, especially the 2022 epidemic, MPXV has emerged as a public health concern. Despite its threat, no specific antiviral drugs have been approved. The viral protein VP39 methyltransferase (MTase) plays a vital role in immune evasion, mRNA capping, and viral replication, making it a promising therapeutic target.
Objective: To analyze and validate the 3D structure and physiochemical properties of VP39 MTase (PDB ID: 8cer) to evaluate its potential as a drug target for anti-MPXV therapies.
Methods: The 3D crystal structure of VP39 MTase was retrieved from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank. Structural validation was performed using Error Recognition and Analysis Tool (ERRAT), verify 3D, and PROCHECK via the SAVES v6.1 server. Physiochemical characteristics were assessed using the ExPASy ProtParam tool.
Results: The ERRAT analysis revealed a 94.39% overall quality factor. Verify 3D indicated 74.91% of residues had an averaged 3D-1D score ≥ 0.1. The Ramachandran plot showed 93.5% of residues in the most favored regions. The protein has a molecular weight of 38.89 kDa, theoretical pI of 9.47, GRAVY score of -0.395, and an aliphatic index of 88.65, suggesting it is hydrophilic and thermostable.
Conclusion: VP39 MTase demonstrates strong structural validity and favorable physiochemical properties, supporting its role as a potential drug target for MPXV. These findings justify further in vitro, in vivo, and molecular dynamics studies for antiviral drug development.
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