A Multiscale Framework for Uncovering Surfactant Mediated Viral Capsid Disruption
Disinfection remains a critical strategy for controlling the transmission of infectious diseases. However, small non-enveloped viruses exhibit exceptional resistance to many disinfectants, often requiring harsh protein-disrupting chemicals for effective inactivation, thereby limiting their applicability in personal care products due to associated side effects. Sodium dodecyl sulphate (SDS) is a widely used anionic surfactant known for its virucidal efficacy; however, the molecular details of its action against robust non-enveloped viruses remain poorly understood, limiting efforts to design safer and more targeted antiviral formulations. In this study, a multiscale simulation approach combining a novel atomic-resolution icosahedral "scaffold framework" and coarse-grained modelling was developed to elucidate the mechanism of SDS-driven disruption of MS2 bacteriophage capsid, a surrogate for non-enveloped viruses. Experimental analyses including dynamic light scattering and transmission electron microscopy revealed that SDS inactivates MS2 in a strongly pH-dependent manner, triggering capsid disassembly at acidic pH while leaving particles largely intact at neutral pH. Molecular dynamics simulations demonstrated that SDS micelles preferentially associate with hexameric pores and inter-dimer clefts under acidic conditions, where protonation of acidic residues weakens the electrostatic network of the capsid surface. Together, these findings provide a detailed molecular framework for SDS virucidal action and highlight the importance of environmental pH in modulating surfactant-virus interactions. These insights offer a foundation for designing next-generation antiviral surfactants with improved efficacy and biocompatibility.