Atomistic insights into the adsorption and interaction of molnupiravir on silver nanoparticles via DFT and molecular dynamics simulations

Abstract Effective antiviral therapy is often limited by poor bioavailability, rapid degradation, and drug resistance. Silver nanoparticles exhibit intrinsic antiviral properties and can enhance the stability and efficacy of drugs. Here, we investigate the adsorption of Molnupiravir on Ag₅₅ clusters using density functional theory (DFT) and molecular dynamics (MD) simulations. DFT calculations reveal strong chemisorption via the O 5 oxygen atom, with an adsorption energy of –4.22 eV and a charge transfer of 0.77 e, producing new hybridized Ag–drug electronic states. Complementary MD simulations in TIP3P water confirm dynamic stability: RMSD and radius of gyration remain steady after 45 ns, and radial distribution functions show a persistent O 5 -Ag coordination peak at ~ 2.6 Å. Interaction-energy decomposition indicates van der Waals forces dominate binding, driving a total nonbonded energy of –885 kJ/mol. Such robust adsorption and Ag polarization could modulate drug release and cytotoxicity. This combined DFT/MD study offers atomistic insight for designing AgNP-based Molnupiravir delivery platforms. Graphical abstract