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primary topic: Stabilizing the shield: C-terminal tail mutation of HMPV F protein for enhanced vaccine design

Stabilizing the shield: C-terminal tail mutation of HMPV F protein for enhanced vaccine design
type: AcademicArticle
type: Article
abstract: Background: Human Metapneumovirus (HMPV) is a respiratory virus in the Pneumoviridae family. HMPV is an enveloped, negative-sense RNA virus encoding three surface proteins: SH, G, and F. The highly immunogenic fusion (F) protein is essential for viral entry and a key target for vaccine development. The F protein exists in two conformations: prefusion and postfusion. The prefusion form is highly immunogenic and considered a potent vaccine antigen. However, this conformation needs to be stabilized to improve its immunogenicity for effective vaccine development. Specific mutations are necessary to maintain the prefusion state and prevent it from changing to the postfusion form. Methods: In silico mutagenesis was performed on the C-terminal domain of the pre-F protein, focusing on five amino acids at positions 469 to 473 (LVDQS), using the established pre-F structure (PDB: 8W3Q) as the reference. The amino acid sequence was sequentially mutated based on hydrophobicity, resulting in mutants M1 (IIFLL), M2 (LLIVL), M3 (WWVLL), and M4 (YMWLL). Increasing hydrophobicity was found to enhance protein stability and structural rigidity. Results: Epitope mapping revealed that all mutants displayed significant B and T cell epitopes similar to the reference protein. The structure and stability of all mutants were analyzed using molecular dynamics simulations, free energy calculations, and secondary structure analysis. Based on the lowest RMSD, clash score, MolProbity value, stable radius of gyration, and low RMSF, the M1 mutant demonstrated superior structural stability. Conclusions: Our findings indicate that the M1 mutant of the pre-F protein could be the most stable and structurally accurate candidate for vaccine development against HMPV.
date: 2025-08
volume: 5
issue: 3
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

MDPI AG
type: Organization

BioMedInformatics
type: Collection

Baldo Oliva
type: Person
given name: Baldo
family name: Oliva

Rohan Gupta
type: Person
given name: Rohan
family name: Gupta

Savitri Tiwari
type: Person
given name: Savitri
family name: Tiwari

Rajeev K Tyagi
type: Person
given name: Rajeev K
family name: Tyagi

Somnath Maji
type: Person
given name: Somnath
family name: Maji

Reetesh Kumar
type: Person
given name: Reetesh
family name: Kumar

Subhomoi Borkotoky
type: Person
given name: Subhomoi
family name: Borkotoky

Jyoti Gupta
type: Person
given name: Jyoti
family name: Gupta

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primary topic: Stabilizing the shield: C-terminal tail mutation of HMPV F protein for enhanced vaccine design