Genome architecture is closely tied to essential biological functions, yet a complete understanding of the mechanisms governing DNA folding remains a significant challenge. Theoretical models based on polymer physics have been applied to decipher the complexity of chromatin architecture and uncover the physical processes shaping its structure. Importantly, recent findings suggest that certain viruses can alter the 3D organization of the host genome. In this review, we highlight recent advances in the development of polymer models used to study how chromatin 3D structure within a cell re-organizes following viral infection, with a particular emphasis on the SARS-CoV-2 virus, capable of altering genome organization of the host cell at different scales, including A/B compartments, TADs and gene-enhancer regulatory contacts.