Joey McTiernan, University of California, Merced

The Assembly and Budding of SARS-CoV_-2

Upon the accumulation of viral structural proteins along the ER-Golgi intermediate compartment (ERGIC), SARS-CoV-2 assembles and buds off, driven by the interactions between these proteins, RNA and the ERGIC membrane. The membrane or M protein is thought to recruit other structural proteins, leading to the formation of protein aggregates and the subsequent induction of membrane curvature, prompting the onset of virion formation. However, the direct impact M protein has on the membrane and how this leads to assembly is unclear. Here, we combine all atom molecular dynamics (MD) simulations of an individual M protein with a mesoscopic continuum model describing the coupled evolution of membrane shape and M protein density to quantify viral assembly and budding. From our MD simulations, we identify the M protein’s ability to thin the membrane and induce curvature dependent on its conformation. By incorporating these properties into our continuum model and then comparing with atomic force microscopy measurements of protein aggregate formation, we estimate the membrane mediated M-M protein interaction and make predictions for the onset of assembly and budding under physiological conditions. This work provides a better understanding of how the interactions and dynamics of M protein lead to viral assembly and budding, supplying insights into alternative methods for preventing viral replication and implications for other enveloped viruses.