Curcumin-based nanomaterials for dual-target inhibition of SARS-CoV-2 omicron main protease and HMPV RNA polymerase: A computational study.

Since the emergence of SARS-CoV-2 in 2020, the world has faced a global pandemic, underscoring the urgent need for next-generation antiviral therapies to address the growing threat of respiratory RNA viruses, including human metapneumovirus (HMPV). In this study, we investigated four green-synthesized carbon-based nanomaterials derived from curcumin, amino (CD1), graphitic (CD2), pyridinic (CD3), and pyrrolic (CD4) forms, as potential dual-target inhibitors of the SARS-CoV-2 Omicron main protease (Mpro) and HMPV RNA-dependent RNA polymerase (RdRp). Molecular docking analyses revealed that these carbon dots (CDs) exhibited higher binding affinities toward both target proteins compared to curcumin and the corresponding approved drugs, namely nirmatrelvir (for Mpro) and remdesivir (for RdRp). Quantum chemical calculations further elucidated the reactivity profiles and interaction potentials of the four CD variants. In addition, molecular dynamics simulations, along with MM-PBSA binding free energy calculations, confirmed the stability of the Mpro-CDs and RdRp-CDs complexes, supporting their potential as dual-target inhibitors. Overall, the results suggest that green-synthesized carbon-based nanomaterials, represent promising candidates for dual-target antiviral strategies, offering a potential pathway for the development of effective treatments against current and emerging viral infections.