Adenovirus DNA polymerase (AdPol)

Adenovirus DNA polymerase (AdPol) is a 140 kDa enzyme encoded by the E2B region of the adenovirus genome, essential for viral DNA replication [3, 4, 8]. It belongs to the Family B (alpha-like) DNA polymerases but is unique in its use of a protein-primed mechanism for the initiation of DNA synthesis [4, 5]. AdPol forms a stable heterodimer with the viral preterminal protein (pTP), which serves as the primer by covalently binding a dCMP residue at the inverted terminal repeats of the linear double-stranded DNA genome [4, 5, 8]. This enzyme is a critical therapeutic target because its inhibition directly halts the production of new viral particles [5]. Clinically, adenovirus infections cause a variety of conditions, including respiratory tract infections, conjunctivitis, and gastroenteritis, which can become life-threatening systemic diseases in immunocompromised patients [1, 3, 6]. Antiviral drugs such as cidofovir and its lipid-linked prodrug brincidofovir target AdPol by acting as nucleotide analogs [1, 2, 3]. These compounds are phosphorylated by host cell kinases and subsequently incorporated into the growing DNA chain by AdPol, leading to chain termination and inhibition of viral replication [2, 3]. However, the clinical utility of these inhibitors is often hampered by significant safety concerns, particularly the dose-limiting nephrotoxicity associated with cidofovir [1].

Other names

DNA-directed DNA polymeraseAdV PolAdenoviral DNA polymeraseE2B DNA polymerase

Inhibition of viral DNA polymerase and DNA chain termination