Human Metapneumovirus Nucleocapsid Inhibitors Discovery for Targeting Viral Replication and Genome Encapsidation: An In Silico Approach.

Human metapneumovirus (HMPV) is a major respiratory pathogen, and its infection is more severe in infants, the elderly, and immunocompromised individuals. Despite its significance, no antiviral drugs are approved to combat HMPV infection. Therefore, it is important to develop drugs that target the nucleocapsid protein, which is crucial for viral replication and genome encapsidation. In this study, computational drug discovery was used to identify new potential molecules targeting the HMPV nucleocapsid protein. In the first step, the virtual screening method was applied to a compound library, and the top three compounds were selected for further redocking using AutoDock Vina. Finally, the chosen compounds were subjected to molecular dynamics simulations, and the stability of the complex and its conformational stability were evaluated using root mean square deviation, root mean square fluctuation, principal component analysis, and binding free energy landscape analysis. Among the chosen compounds, 24,330,502, 24,292,974, and 17,515,455 showed high binding affinity, stability, and conformational stability, and their results were better than those of the reference compound, Gamma-Fagarine, and they retained the ligands in the binding pocket with high stability. Therefore, the results of the present study reveal that the selected compounds, namely, 24,330,502, 24,292,974, and 17,515,455, have the potential to inhibit the HMPV nucleocapsid protein and are thus important for the treatment of HMPV infection.