Molecular architecture and dynamics of SARS-CoV-2 envelope by integrative modeling

Despite tremendous efforts, the exact structure of SARS-CoV-2 and related betacoronaviruses remains elusive. SARS-CoV-2 envelope is a key structural component of the virion that encapsulates viral RNA. It is composed of three structural proteins, spike, membrane (M), and envelope, which interact with each other and with the lipids acquired from the host membranes. Here, we developed and applied an integrative multi -scale computational approach to model the envelope structure of SARS-CoV-2 with near atomistic detail, focusing on studying the dynamic nature and molecular interactions of its most abundant, but largely under-studied, M protein. The molecular dynamics simulations allowed us to test the envelope stability under different configurations and revealed that the M dimers agglomerated into large, filament-like, macromolec-ular assemblies with distinct molecular patterns. These results are in good agreement with current experi-mental data, demonstrating a generic and versatile approach to model the structure of a virus de novo.

Automated summary

Despite efforts, the exact structure of SARS-CoV-2 and related betacoronaviruses remains unknown. This study developed a computational approach to model the envelope structure of SARS-CoV-2 with near atomistic detail and focused on the understudied M protein. Molecular dynamics simulations revealed the agglomeration of M dimers into large macromolecular assemblies with distinct patterns, in agreement with experimental data, demonstrating a versatile approach for de novo virus structure modeling.