Modeling the assembly of curvature inducing proteins in SARS-CoV-2 budding at multiple scales

The assembly of SARS-CoV-2 in the ER-Golgi intermediate compartment (ERGIC) is a result of the interplay between the virus' accumulated structural proteins and the ERGIC membrane. As the most abundant structural protein, the membrane (M) protein is thought to interact with the envelope (E), nucleocapsid (N), and spike (S) proteins and plays a key role in producing sufficient curvature for viral budding. Experimentally, it has been shown that M proteins phase separate with a combination of N proteins and RNA in solvent, possibly mediating the onset of budding in the presence of a membrane. This phase separation can be demonstrated analytically by modeling the coupled evolution of M protein density and membrane shape, where proper parameterization requires a microscopic understanding of the interactions and dynamics of M proteins. To help develop this understanding, we utilize a multiscale modeling approach. From mesoscale, continuum models of membrane-bound M protein dimers, we show the impact of different protein properties on the budding process. Additionally, we present estimates of parameters needed for our mesoscopic model using all-atom simulations of M protein dimers, both free and bound in the membrane. Combining the parameters determined from all-atom simulations with our mesoscopic model allows for improved understanding of the budding and assembly process for SARS-CoV-2.