Comparing elastic and molecular models of membrane bending local to SARS-CoV-2 envelope protein for mechanistic understanding.

Abstract

The Envelope (E) protein of SARS-CoV-2 is an ion channel that plays several roles in the viral lifecycle, including the induction of membrane curvature during the budding process. While its function as a viroporin has been explored by several labs, the precise mechanism through which the E protein controls membrane bending is not presently understood. In the present study, we show that the E protein induces membrane bending in silico in coarse-grain molecular dynamics (CG-MD) simulations, suggesting that the computational microscope is a promising means for exploring this phenomenon further. We quantify the extent and type of membrane bending present in systems with varying membrane thickness, lipid saturation, protein structure, and protein concentration using our CG-MD analysis suite nougat. We then compare those results with theoretical predictions from a continuum membrane model that treats each leaflet as an elastic surface with bulk properties. These comparisons allow us to gain insight into the bending mechanism of the E protein. The results have implications for membrane biophysics and lays the groundwork for further research on the efficacy of drug candidates that target the SARS-CoV-2 E protein.