Cytomegalovirus DNA terminase complex protein pUL56 (pUL56)

Cytomegalovirus DNA terminase complex protein pUL56 is a critical component of the Human Cytomegalovirus (HCMV) replication machinery, serving as the large subunit of the viral terminase complex alongside pUL89 and pUL51 (UniProt: P06488). Its primary biological function is to facilitate the cleavage of concatemeric viral DNA into individual genomic units and drive their translocation into preformed viral capsids using its intrinsic ATPase activity (Goldner et al., 2011, PubMed: 21859831). Because this DNA packaging process is unique to herpesviruses and lacks a human homolog, pUL56 represents a highly specific and effective therapeutic target for antiviral intervention. The drug letermovir (Prevymis) is a first-in-class inhibitor that binds to the pUL56 subunit, effectively blocking the production of infectious progeny virions (FDA Label: Prevymis). Clinical utility is primarily focused on the prevention of HCMV infection and disease in immunocompromised individuals, such as hematopoietic stem cell transplant recipients. However, the emergence of resistance mutations within the UL56 gene, particularly at codons 236 and 325, remains a significant therapeutic challenge (Lix et al., 2020, PubMed: 32152231). Overall, pUL56 is a validated target that has shifted the paradigm of HCMV management from broad-spectrum DNA polymerase inhibition to highly specific terminase inhibition.

Other names

UL56Large terminase subunitDNA packaging protein UL56HCMV pUL56Human herpesvirus 5 UL56

Inhibition of the viral DNA terminase complex, preventing the cleavage of concatemeric DNA and its packaging into viral capsids.