Computational Analysis of Bioactive Compounds from Black Pepper (Piper nigrum L.) as Potential Inhibitors of Human Metapneumovirus (HMPV) Replication Protein

Human metapneumovirus (HMPV) is a significant respiratory pathogen responsible for acute respiratory infections (ARIs) globally, with severe impacts on infants, the elderly, and immunocompromised individuals. Despite its clinical burden, no specific antiviral therapies or vaccines have been approved to date. This study aimed to explore the antiviral potential of bioactive compounds from Piper nigrum L. (black pepper)—namely caryophyllene, chavicine, eugenol, piperidine, and piperine—targeting the HMPV phosphoprotein, a key cofactor in the viral replication complex. A structure-based computational approach was employed, comprising molecular docking using the CB-Dock2 to assess ligand–protein binding interactions and pharmacokinetic and toxicity profiling using ADMETsar 3.0. Ribavirin, a broad-spectrum antiviral agent, was used as a positive control to benchmark compound performance. Docking results identified chavicine as the most promising compound, with a binding affinity of –7.4 kcal/mol to the HMPV phosphoprotein, followed by piperine (–6.4 kcal/mol), both comparable to ribavirin. ADMET predictions indicated favorable absorption and metabolic properties, but both compounds showed potential hepatotoxicity, nephrotoxicity, and cytochrome P450 interactions, highlighting the need for cautious interpretation. In conclusion, chavicine and piperine demonstrate promising in silico antiviral activity against HMPV and merit further investigation. However, these findings are based solely on computational models, and future in vitro and in vivo studies are essential to validate their efficacy and safety for therapeutic development.