In silico prediction, molecular docking and simulation of natural flavonoid apigenin and xanthoangelol E against human metapneumovirus.

Human metapneumovirus (hMPV) is one of the potential pandemic pathogens, and it is a concern for elderly subjects and immunocompromised patients. There is no vaccine or specific antiviral available for hMPV. We conducted an in-silico study to predict initial antiviral candidates against human metapneumovirus. Our methodology included protein modeling, stability assessment, molecular docking, molecular simulation, analysis of non-covalent interactions, bioavailability, carcinogenicity, and pharmacokinetic profiling. We pinpointed four plant-derived bio-compounds as antiviral candidates. Among the compounds, apigenin showed the highest binding affinity, with values of - 8.0 kcal/mol for the hMPV-F protein and - 7.6 kcal/mol for the hMPV-N protein. Molecular dynamic simulations and further analyses confirmed that the protein-ligand docked complexes exhibited acceptable stability compared to two standard antiviral drugs. Additionally, these four compounds yielded satisfactory outcomes in bioavailability, drug-likeness, and ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) and STopTox analyses. This study highlights the potential of apigenin and xanthoangelol E as an initial antiviral candidate, underscoring the necessity for wet-lab evaluation, preclinical and clinical trials against human metapneumovirus infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-025-00539-7.