Functional and structural insights into HCMV terminase accessory proteins pUL77 and pUL93

Human cytomegalovirus (HCMV) remains a significant health concern, particularly for immunocompromised individuals and in cases of congenital infection. The emergence of resistance to current antivirals targeting viral polymerase has necessitated the development of novel therapeutic approaches. Letermovir, which targets the HCMV terminase complex, represents a promising alternative. However, a deeper understanding of the virus's structural components and their interactions is crucial for identifying new potential drug targets. Here, we focused on two proteins, pUL77 and pUL93, which are associated with the viral capsid and interact with the terminase complex. By analyzing their polymorphism, structure, and functional motifs, we identified essential nuclear localization motifs and conserved regions in these proteins, providing valuable insights for the development of innovative anti-HCMV strategies, such as inhibitory peptides, which could complement existing treatments and address the ongoing challenge of antiviral resistance.