Adenovirus 5 DNA polymerase (Ad5 DNA Pol)

Adenovirus 5 DNA polymerase is a 140 kDa enzyme essential for the replication of the human adenovirus type 5 (Ad5) genome (UniProt: P04495). It belongs to the Family B (alpha-like) DNA polymerases and utilizes a unique protein-priming mechanism involving the preterminal protein (pTP) to initiate DNA synthesis (PubMed: 11537141). The enzyme possesses both 5'-3' polymerase activity and 3'-5' exonuclease activity for proofreading, ensuring high-fidelity replication via a strand displacement mechanism (Wikipedia: Adenovirus). As a critical component of the viral replication machinery, it is a primary target for antiviral therapy, particularly in immunocompromised patients where adenovirus can cause life-threatening systemic infections (NIH: PMC6694862). Drugs such as cidofovir target this polymerase by acting as nucleotide analogues that inhibit DNA synthesis and cause chain termination, although their use is often limited by significant side effects like nephrotoxicity (PubMed: 30642897). Resistance to these drugs can emerge through specific mutations within the polymerase gene, complicating long-term treatment (PubMed: 12225364). Research continues into more potent and less toxic inhibitors, such as brincidofovir, to improve clinical outcomes for severe adenoviral disease (NIH: PMC6694862).

Other names

Adenovirus type 5 DNA polymeraseHuman adenovirus 5 DNA polymeraseAd PolPOLDNA-directed DNA polymerase

Nucleoside/nucleotide analogue inhibition; competitive inhibition of dNTP binding and non-obligate chain termination of the nascent DNA strand.