J Mol Graph Model. 2025 Aug 5;141:109130. doi: 10.1016/j.jmgm.2025.109130. Online ahead of print.
ABSTRACT
The Marburg virus, a close relative of the Ebola virus, is a menacing Filovirus known for its devastating outbreaks in Germany and recent outbreaks in Guinea and Tanzania. This deadly pathogen triggers severe hemorrhagic fever, posing a grave threat to public health and demanding urgent attention from the global medical community. The amino acid sequence and PDB of the Envelope glycoprotein (GP) were extracted from RCSB for use in predicting epitopes (IEDB server). The construction of the multi-epitope vaccine included an adjuvant and linkers (AAY, EAAAK, GPGPG), which were assessed with the ProtParam tool to characterize their physico-chemical properties. Additionally, modeling was carried out with the Robetta server, and the modeled vaccine was docked with Toll-like receptor 4 (TLR4). Finally, immune and molecular dynamic simulations were implemented using the C-ImmSim and GROMACS packages. The final multi-epitope vaccine consists of 211 amino acids, created with 5 CTL and 4 HTL epitopes that were validated and passed assessments for antigenicity, allergenicity, and toxicity. The modeled multi-epitope vaccine was evaluated and demonstrated high model quality. The best molecular docking candidate was selected and evaluated using PDBsum. Subsequently, by assessing RMSD, RMSF, and Gyration, the molecular dynamic simulation revealed considerable binding with TLR4, and the complex remained stable throughout the simulation. Ultimately, the multi-epitope vaccine can stimulate both humoral and cell-mediated immune responses, validated computationally. The overall implication of this investigation shows the potency of the multi-epitope construct as an efficient protective vaccine against the Marburg virus.
PMID:40782386 | DOI:10.1016/j.jmgm.2025.109130
