Effect of Cationic Surfactants on the Molecular Organization of the Simplified Model Lipid Envelope of SARS-CoV-2 Virus─Insights from the Langmuir Monolayer and Liposome Studies.

In this study, we compare the physicochemical interactions of cationic surfactants, cetyltrimethylammonium bromide (CTAB) and cetylpyridinium chloride (CPC), at concentrations lower than their CMC with model systems mimicking the lipidic content of the SARS-CoV-2 envelope in terms of the charge of polar heads and the composition of acyl chains. The DOPC/DMPS/PI 50:35:15 (molar ratio) Langmuir monolayers treated as 2D models exhibited increased fluidity and a shift of surface pressure-area per molecule isotherms toward larger areas upon surfactant interaction. Liposomes (3D models) showed an increase in hydrodynamic diameter and changes in zeta potential in the presence of CTAB and CPC. These effects were observed both in water and PBS buffer (pH 7.4), while in PBS the changes were more pronounced in the monolayer systems and surfactant-dependent for liposomes. Additionally, giant unilamellar vesicles (GUVs) were prepared and visualized using fluorescence microscopy to follow shape fluctuations and rapid changes in fluorescence intensity upon exposure to surfactants. Despite the electrostatic attractions governing the lipid envelope-surfactant interactions, the differences in the interaction mechanisms arise from the molecular structure of the polar headgroups of surfactants: CPC is more likely to effectively penetrate into the lipid layers due to its planar, aromatic headgroup, while CTAB's bulky polar head leads to its accumulation close to the lipid surface. These findings provide new insights into molecular-level interactions between low-concentration cationic surfactants and more exact models of viral lipid envelopes and may serve as a basis for the development of mutation-independent antiviral strategies targeting the lipid components of enveloped viruses.