Molecular Dynamics Study of The Lysozyme-Based Drug Delivery Nanosystems Loaded with Antiviral Drugs and Cyanine Dyes

Protein-based drug nanocarriers are increasingly recognized as promising candidates for effective drug delivery, owing to a multitude of beneficial advantages over synthetic materials including low cytotoxicity, biocompatibility, biodegradability, abundance, renewability, and high drug loading capacity mediated by diverse functional groups and interactions. In the present study the molecular dynamics simulation was employed to explore the stability of lysozyme-based drug delivery nanosystems functionalized by the antiviral drugs (favipiravir, molnupiravir, nirmatrelvir and ritonavir) and cyanine dyes (AK7-5, AK5-6, AK3-11). A series of 5 ns or 100 ns MD simulations for the top-scored docked drug-dye-protein complexes, obtained using the PatchDock server was performed at 310 K with GROMACS software using the CHARMM General Force Field. The MD results have been analyzed in terms of the parameters, such as the backbone root mean-square deviation, gyration radius, solvent accessible surface area, the root means square fluctuations. The analysis of calculated parameters for the studied systems enabled us to improve the previously acquired molecular docking data. Taken together, the results obtained indicate that Lz-F-AK3-11, Lz-R-AK75, Lz-R-AK56, Lz-N-AK75, Lz-N-AK3-11, and Lz-M-AK75 systems exhibit the highest stability among the examined dye-drug-protein systems and represent potential candidates for the targeted delivery of the explored antiviral agents.