Molecular Docking Assessment of Antiviral Potential of Tea Formulated from Local Spices against Human Metapneumovirus (hMPV)

Human metapneumovirus (hMPV) is a globally significant respiratory pathogen with no approved specific antiviral treatment. This study conducted an in silico biochemical evaluation of eleven bioactive compounds derived from local culinary spices, aiming to identify potential therapeutic agents against hMPV. Physicochemical profiling revealed that compounds such as β-caryophyllene, squalene, and stigmasterol exhibited high lipophilicity (log P > 4.5), low topological polar surface area (TPSA < 30 ?²), and zero hydrogen bond donors/acceptors, suggesting strong membrane permeability and potential interaction with viral lipid envelopes. Conversely, hydrophilic compounds like glucaric acid and mannitol demonstrated high TPSA (>90 ?²) and multiple hydrogen bonding sites, which, while limiting membrane permeability, may contribute to immunomodulatory effects. Molecular docking in this study indicated that squalene (?19.6 kcal/mol) and stigmasterol (?11.2 kcal/mol) had the highest binding affinities towards hMPV Toll-Like receptor-4, (a glycoprotein that primarily recognizes the viral Fusion protein), driven primarily by hydrophobic and van der Waals interactions. Pharmacokinetic predictions showed favorable gastrointestinal absorption across most compounds, with minimal P-glycoprotein interaction and negligible cytochrome P450 inhibition, reducing the risk of drug-drug interactions. Toxicity assessments predicted non-mutagenicity and non-cytotoxicity for all compounds; however, squalene and stigmasterol showed minimal neurotoxicity, cardiotoxicity, and immunotoxicity, warranting further formulation strategies to mitigate any adverse outcome. Drug-likeness evaluation, based on Lipinski’s Rule of Five and Veber’s criteria, identified β-caryophyllene, vanillin derivatives, and glucaric acid as optimal candidates due to their balance of solubility, permeability, binding efficiency, and safety. The predicted LD50 for most compounds was 1190 mg/kg, classifying them as moderately safe. These findings support the potential of local spice-derived phytocompounds as therapeutic leads against hMPV, with β-caryophyllene and vanillin derivatives recommended for further experimental validation. These findings reinforce the position that natural compounds with suitable structural features can interact effectively with both viral and immunological targets, offering a dual mechanism of antiviral action direct inhibition and immune modulation. While this research establishes a foundation for the development of