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Repurposing Metal-Based Therapeutics for Human Metapneumovirus (HMPV): An Integrative Computational Approach

Dubey, A.; Kumar, M.; Tufail, A.; Dwivedi, V. D.

2025-01-15 bioinformatics
10.1101/2025.01.14.632891 bioRxiv
Show abstract

Human metapneumovirus (HMPV) poses a significant global health challenge, with limited therapeutic options available. This study employs a comprehensive computational framework to repurpose metal-based drugs as potential HMPV inhibitors. A library of compounds was systematically evaluated using virtual screening, high-precision molecular docking, molecular dynamics (MD) simulations, density functional theory (DFT) calculations, molecular electrostatic potential (MESP) mapping, and pharmacophore modeling. Key candidates, including Auranofin, Silver Sulfadiazine, and Gallium Nitrate, demonstrated high binding affinities ({Delta}Gbinding: -68.5 to -62.7 kcal/mol) and favorable stability metrics (RMSD: 2.1-2.4 [A]). ADME-toxicity (ADMET) profiling highlighted Auranofins robust bioavailability (80%) and extended half-life (8.5 hours), while Ribavirin and Favipiravir emerged as safe controls with minimal toxicity. Quantum chemical analyses reinforced the compounds electronic stability and reactivity. This integrative study provides a promising avenue for repurposing existing therapeutics, bridging computational insights with translational potential to combat HMPV.

Published in Bioinorganic Chemistry and Applications · not in our set (fewer than 10 published preprints to learn from) · training set

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