Viral DNA packaging ATPase (TerL)

The Viral DNA packaging ATPase is a highly conserved enzyme essential for the replication and assembly of various viruses, most notably large double-stranded DNA (dsDNA) viruses such as herpesviruses, poxviruses, and adenoviruses, as well as some RNA viruses like enteroviruses. It functions as the motor component of the viral terminase complex, utilizing the energy from ATP hydrolysis to translocate the viral genome into a preformed protein capsid. This process, often referred to as "genome packaging" or "stuffing," is a critical late-stage step in the viral life cycle. Because these viral ATPases are structurally distinct from human cellular ATPases, they represent attractive targets for highly specific antiviral therapies with low toxicity. The most prominent drug targeting this enzyme is Letermovir, which is FDA-approved for the prevention of cytomegalovirus (CMV) infection. Other experimental inhibitors are being developed to target the ATPase activity of proteins like the enterovirus 2C protein and the SARS-CoV-2 nsp13 helicase, highlighting the broad therapeutic potential of targeting viral ATP-dependent motors.

Other names

Terminase large subunitDNA packaging motorpUL56pUL15A32L2C proteingp17gp16IVa2Virion-packaging ATPase

Inhibition of the viral terminase complex or specific non-structural proteins, blocking the ATP-dependent translocation of the viral genome into the procapsid and preventing the formation of infectious virions.