Abstract
Despite advances in COVID-19 vaccines and antivirals, SARS-CoV-2 remains a significant public-health threat. While handwashing helps prevent infection, the anti-SARS-CoV-2 activity of anionic surfactants in hand soaps has not been systematically evaluated. In this study, we compared five surfactants: potassium oleate (C18:1-K), potassium myristate (C14:0-K), potassium laurate (C12:0-K), sodium laureth sulfate (SLES), and sodium dodecyl sulfate (SDS). Viral infectivity assays demonstrated that C18:1-K exhibited remarkable efficacy, reducing SARS-CoV-2 infectivity by more than 10⁵-fold at a concentration of 1 mM. In contrast, SDS achieved only about a 10¹-fold reduction, and both SLES and C12:0-K showed minimal activity. Isothermal titration calorimetry revealed that C18:1-K-virus interactions exhibited a positive enthalpy change (ΔH), indicating endothermic hydrophobic interactions with viral-envelope lipids-contrasting with the results observed for influenza virus. By contrast, SDS and C12:0-K interactions showed negative ΔH values, suggesting exothermic electrostatic interactions with viral surface proteins. Transmission electron microscopy revealed extensive "rupture" images of viral particles after treatment with SDS or C12:0-K, whereas no such image was observed with C18:1-K. All surfactants induced concentration-dependent viral aggregation, suggesting that aggregation also contributes to viral inactivation. Among the surfactants tested, C18:1-K, which demonstrated the highest antiviral activity, also had the lowest critical micelle concentration, suggesting that hydrophobic interactions become pronounced above this threshold. These findings suggest that the inactivation mechanisms of SARS-CoV-2 vary according to the physicochemical properties of the surfactants. Surfactants with strong hydrophobic interaction capabilities may exert superior antiviral effects, offering insights for the rational design of effective disinfectants.