β-Escin interactions with lipid membranes: Role of lipid composition and impact on SARS-CoV-2 E protein transmembrane domain localization

Cholesterol drives E-protein depth redistribution via a matrix-mediated helix tilt adjustment. • Escin-induced peptide localization shifts strictly require the presence of charged DMPS lipids. • Escin is hypothesized to modulate the viroporin conformation via localized helix kinking rather than matrix disruption. • Escin is able to extract cholesterol from lipid membrane. β-Escin is a well-known saponin derived from the horse chestnut tree. Saponins, including escin, exhibit a wide range of biological activities, among which membrane-modifying activity is particularly notable. The latter is key to understanding the molecular mechanisms underlying escin's biological effects, including its antiviral properties. For example, altering membrane properties can strongly influence the life cycle of enveloped viruses such as SARS-CoV-2 by modulating the activity of its envelope protein (E protein). In the present paper, we studied the localization of both escin and the E protein transmembrane domain (ETM) in model membranes with different lipid compositions. We demonstrated that escin can alter ETM localization in membranes containing the negatively charged lipid DMPS, and that escin is also capable of extracting cholesterol from model lipid membranes. Download: Download high-res image (423KB) Download: Download full-size image