Unraveling the Antiviral Efficacy of Surfactants: Deactivation of Nonenveloped Viruses through Synergistic Electrostatic Mechanisms.

viral load reduction was achieved using anionic surfactants at pH < 5 or cationic surfactants at pH > 10. Dynamic and electrophoretic light scattering provided data on surfactant-capsid interactions, which we further explored by molecular modeling of the capsid charge distributions across pH ranges using protein sequence data. These results informed a selective-permeation model describing how surfactant efficacy depends on electrostatic interactions─repulsion, attraction, and permeation─with capsid proteins. The model predictions were validated using transmission electron microscopy and were applied to accurately predict the pH inactivation thresholds of ΦX174 phage. The results indicate that both cationic and anionic surfactants could serve as efficient antiviral agents, if the pH of the system favors surfactant penetration through both the inner and outer layers of the capsids. They offer a theoretical framework for the rational design of antiviral formulations for NEVs.