Despite tremendous efforts by research community during the COVID-19 pandemic, the exact structure of SARS-CoV-2 and related betacoronaviruses remains elusive. Here, we developed and applied an integrative multi-scale computational approach to model the envelope structure of SARS-CoV-2, focusing on studying the dynamic nature and molecular interactions of its most abundant, but largely understudied, M (membrane) protein. The molecular dynamics simulations allowed us to test the envelop stability under different configurations and revealed that M dimers agglomerated into large, filament-like, macromolecular assemblies with distinct molecular patterns formed by M’s transmembrane and intra-virion (endo) domains. These results were in agreement with the experimental data, demonstrating a generic and versatile integrative approach to model the structure of a virus de novo, providing insights into critical roles of structural proteins in the viral assembly and integration, and proposing new targets for the antiviral therapies.