In Silico Structural and Functional Characterization of the HMPV M2-1 Protein Reveals Its Potential as a Therapeutic Target

Authors

  • Saifullah Sarkar Department of Agriculture, Gopalganj Science and Technology University, Gopalganj-8100, Bangladesh Author https://orcid.org/0009-0009-5259-3809
  • Sanjay Das Department of Agriculture, Gopalganj Science and Technology University, Gopalganj-8100, Bangladesh Author
  • Md. Hasan Ali Department of Agriculture, Gopalganj Science and Technology University, Gopalganj-8100, Bangladesh Author https://orcid.org/0009-0004-7710-4286

DOI:

https://doi.org/10.71193/jmct.20250008

Keywords:

Human metapneumovirus (HMPV), Pneumovirus matrix protein 2 (M2), In  silico, Homology modeling, Molecular docking

Abstract

Human metapneumovirus (HMPV) is a leading cause of acute respiratory infections in children, the elderly, and immunocompromised individuals, yet no licensed antivirals or vaccines exist. This study employed in-silico approaches to characterize the HMPV M2-1 protein, a key regulator of viral transcription, and to identify potential natural inhibitors. Physicochemical analysis revealed that M2-1 is a hydrophilic, thermally stable, and basic protein with properties favorable for RNA binding and transcriptional regulation. Conserved domain and motif analyses identified a transcription processivity factor and a zinc finger C3H1 motif, confirming its role in RNA stabilization. Gene Ontology and protein–protein interaction analyses positioned M2-1 as a multifunctional protein associated with viral replication, assembly, and host immune modulation. Homology modeling using SWISS-MODEL and I-TASSER generated high-quality 3D structures, with the SWISS-MODEL showing superior stereochemical quality and enabling accurate active site prediction. CASTpFold analysis revealed 22 potential binding pockets, with the largest active site measuring 279.006 ų. Molecular docking using AutoDock Vina in PyRx with 58 garlic (Allium sativum) compounds identified IMPHY010911 as the most potent binder (-7.7 kcal/mol). These findings highlight M2-1 as a promising antiviral drug target and suggest garlic bulb-derived phytochemicals may serve as potential natural inhibitors against HMPV infection.

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2025-11-29

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How to Cite

Saifullah Sarkar, Sanjay Das, & Ali, M. H. (2025). In Silico Structural and Functional Characterization of the HMPV M2-1 Protein Reveals Its Potential as a Therapeutic Target. Journal of Medicinal Chemistry and Therapeutics, 2(01), 1-11. https://doi.org/10.71193/jmct.20250008

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