Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 28, 2025

Introduction Leptospirosis, caused by Leptospira interrogans , is a neglected zoonotic disease that poses significant global health risk to both humans and animals. The rise of antimicrobial resistance the inefficacy existing vaccines highlight urgent need for new preventive strategies. Methods An immunoinformatics approach was employed design multi-epitope subunit vaccine (MESV) against leptospirosis. B-cell, cytotoxic T lymphocyte (CTL), helper (HTL) epitopes were selected from five key proteins. These fused with heparin-binding hemagglutinin (HBHA) adjuvant appropriate linkers construct broad-spectrum vaccine. physicochemical properties assessed, including antigenicity, immunogenicity, allergenicity, conservation. vaccine’s 3D structure modeled, optimized, validated. Molecular docking, molecular dynamics simulations, MM-GBSA analysis performed assess vaccine's binding interactions Toll-like receptors (TLR2 TLR4). Immune simulations in silico cloning also conducted evaluate immune response expression potential. Results MESV demonstrated high non-allergenicity, conservation across different strains. Population coverage revealed T-cell significantly interacted HLA molecules, covering 95.7% population. docking showed strong stable TLR2 TLR4, energies -1,357.1 kJ/mol -1,163.7 kJ/mol, respectively. confirmed stability these accurately calculated intermolecular free energies. indicated robust B cell responses, could be successfully expressed E. coli . Discussion findings suggest promising candidate leptospirosis prevention, providing responses broad population coverage. However, further vivo studies are necessary validate its efficacy safety.

Language: Английский

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HIT-EC: Trustworthy prediction of enzyme commission numbers using a hierarchical interpretable transformer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Abstract Accurate and trustworthy prediction of Enzyme Commission (EC) numbers is critical for understanding enzyme functions their roles in biological processes. Despite the success recently proposed deep learning-based models, there remain limitations, such as low performance underrepresented EC numbers, lack learning strategy with incomplete annotations, limited interpretability. To address these challenges, we propose a novel hierarchical interpretable transformer model, HIT-EC, number prediction. HIT-EC employs four-level architecture that aligns structure leverages both local global dependencies within protein sequences this multi-label classification task. We also to handle numbers. an evidential produces predictions by providing domain-specific evidence through biologically meaningful interpretation scheme. The predictive was assessed multiple experiments: cross-validation large dataset, validation external data, species-based evaluation. showed statistically significant improvement when compared current state-of-the-art benchmark models. HIT-EC’s robust interpretability further validated identifying well-known conserved motifs functional regions CYP106A2 family. would be robust, interpretable, reliable solution prediction, implications enzymology, drug discovery, metabolic engineering. open-source code publicly available at: https://github.com/datax-lab/HIT-EC .

Language: Английский

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Investigating the Antimicrobial, Antidiabetes, and Antioxidant Potential of Hydroxyl‐Containing Schiff Bases, In Vitro, and Computational Studies

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(7)

Published: Feb. 1, 2025

Abstract Four azomethine compounds ( L 1 –L 4 ) derived from the reaction of p ‐hydroxybenzaldehyde and various primary amines are reported herein. Various analytical spectroscopic techniques were employed to characterize synthesized compounds. The antidiabetic properties evaluated by exploring α‐amylase α‐glucosidase assays, where 2 3 displayed good with an IC 50 values 0.06 0.03 mg/ml for assay, respectively, better than acarbose (standard drug) value 0.08 mg/ml. With exception L4, antioxidant activity showed nitric oxide radical scavenging capacity their significant DPPH free ability. antibacterial activities dose‐dependent, notable activities. Computational studies using density functional theory molecular docking methods indicated that had energy gap 7.10 eV, making it least reactive, while 6.52 most chemically reactive.

Language: Английский

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Function assignment and identification of potential lead compounds for the putative protein AXA72_03280 of Mycoplasmoides pneumoniae

Next research., Journal Year: 2025, Volume and Issue: unknown, P. 100282 - 100282

Published: March 1, 2025

Language: Английский

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Designing a multi-epitope vaccine against Pseudomonas aeruginosa via integrating reverse vaccinology with immunoinformatics approaches

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 26, 2025

Pseudomonas aeruginosa is a typically opportunistic pathogen responsible for wide range of nosocomial infections. In this study, we designed two multi-epitope vaccines targeting P. proteins, incorporating cytotoxic T lymphocyte (CTL), helper (HTL), and linear B (LBL) epitopes identified using reverse vaccinology immunoinformatics approaches. The exhibited favorable physicochemical properties, including stability, solubility, optimal molecular weight, suggesting their potential as viable candidates vaccine development. Molecular docking studies revealed strong binding affinity to Toll-like receptors 1 (TLR1) 2 (TLR2). Furthermore, dynamics simulations confirmed the stability vaccine-TLR complexes over time. Immune simulation analyses indicated that could induce robust humoral cellular immune responses, providing promising new approach combating infections, particularly in face increasing antibiotic resistance.

Language: Английский

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Molecular and Computational Insights into algD Biofilm Genes in Multi Drug Resistant and Extensively Drug Resistant Pseudomonas aeruginosa

Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: 205, P. 107634 - 107634

Published: April 28, 2025

Language: Английский

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