Molecular Dynamics Insights into the Adsorption of the COVID-۱۹ Antiviral Remdesivir on Silica-Functionalized Graphene Oxide: Enthalpic Prevalence and Comparative Evaluation for Targeted Antiviral Delivery

Remdesivir, a broad-spectrum antiviral agent, has gained widespread attention for treating SARS-CoV-۲; however, its therapeutic efficacy remains limited by poor solubility, rapid metabolism, and inefficient delivery. In this study, we employed all-atom molecular dynamics simulations to investigate the adsorption behavior of Remdesivir on a silica-functionalized graphene oxide (GO–SiNP) nanocarrier. The GO–SiNP hybrid integrates the π-conjugated structure and high surface area of graphene oxide with the surface reactivity and aqueous dispersibility of silica nanoparticles, enabling robust non-covalent interactions through hydrogen bonding, π–π stacking, and van der Waals forces. Radial distribution functions indicated a higher molecular affinity in the GO–SiNP system, with a closer peak proximity (~۰.۲۸ nm), while RMSD and RMSF analyses showed enhanced conformational stability of the drug at the hybrid interface. Key descriptors of drug–carrier interactions—including RDFs, structural fluctuation, and MM-PBSA binding energies—demonstrated increased interaction persistence and enthalpic prevalence in the GO–SiNP system. The selection of an appropriate partial charge model was found to critically affect the electrostatic interactions and overall binding behavior of Remdesivir with the GO–SiNP nanocarrier. A comparative evaluation with other nanocarriers revealed that GO–SiNP exhibited the most favorable binding affinity (−۴۱.۸ ± ۱.۶ kcal/mol), highlighting its superior potential for antiviral drug delivery. These findings emphasize the importance of tailored surface functionalization in optimizing drug–carrier interactions and support the GO–SiNP hybrid as a promising platform for stable, high-affinity antiviral delivery systems.

Keywords:

Remdesivir adsorption , Graphene oxide–silica hybrid , Drug-carrier interaction , Surface functionalization , Molecular Simulation , Binding Free Energy Analysis