Natural flavonoid apigenin and xanthoangelol E are potent antivirals against human metapneumovirus: an in-silico study

Abstract 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 develop antivirals 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 significantly 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 highest potential of apigenin and xanthoangelol E as effective antivirals, underscoring the necessity for preclinical and clinical trials and wet-lab evaluation to consider them as treatments for human metapneumovirus infection.