Human adenovirus DNA polymerase (HAdV Pol) (HAdV Pol)

Human adenovirus DNA polymerase (HAdV Pol) is a 140-kDa enzyme essential for the replication of the adenovirus double-stranded DNA genome (UniProt: P03261). It belongs to the B-family of DNA polymerases and exhibits both 5'-3' DNA-directed DNA polymerase activity and 3'-5' exonuclease proofreading activity to ensure high-fidelity genome duplication (PubMed: 21835785). A distinguishing feature of this enzyme is its use of a protein-priming mechanism, where it interacts with the viral pre-terminal protein (pTP) to initiate DNA synthesis rather than using an RNA primer (NIH: PMC3150760). HAdV Pol is a critical therapeutic target for treating severe adenovirus infections, which pose significant risks to immunocompromised patients, including those undergoing hematopoietic stem cell transplantation (PubMed: 30731145). Antiviral agents such as cidofovir and its lipid-conjugate prodrug, brincidofovir, target this enzyme; these nucleotide analogs are incorporated into the nascent DNA chain, leading to chain termination or the production of non-functional viral genomes (PubChem: CID 60613). However, the clinical utility of these drugs is frequently limited by significant safety concerns, most notably dose-limiting nephrotoxicity, and the potential for the virus to develop resistance through specific mutations within the polymerase gene (PubMed: 25332146).

Other names

Adenovirus DNA polymeraseAdPolDNA-directed DNA polymeraseAdenoviral DNA polymerasepPol

Inhibition of viral DNA synthesis through competitive inhibition with natural deoxynucleotides and subsequent DNA chain termination upon incorporation into the viral DNA strand.