A Multiscale Framework for Uncovering Surfactant Mediated Viral Capsid Disruption

Masirevic, S.; Marzinek, J. K.; Kong, M. L. Y.; Lin, G.; Chen, H.; Liu, J.; Chua, C.; Maupin, C. M.; Verma, C. S.; Fox, S. J.; Bond, P. J.

doi:10.1101/2025.06.16.659739

bioRxiv · 10.1101/2025.06.16.659739

A Multiscale Framework for Uncovering Surfactant Mediated Viral Capsid Disruption

Masirevic, S.·Marzinek, J. K.·Kong, M. L. Y.·Lin, G.·Chen, H.·Liu, J.·Chua, C.·Maupin, C. M.·Verma, C. S.·Fox, S. J.·Bond, P. J.

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Abstract

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.

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Masirevic, S., Marzinek, J. K., Kong, M. L. Y., Lin, G., Chen, H., Liu, J., Chua, C., Maupin, C. M., Verma, C. S., Fox, S. J., Bond, P. J.. 2025-06-17. A Multiscale Framework for Uncovering Surfactant Mediated Viral Capsid Disruption. https://doi.org/10.1101/2025.06.16.659739

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