Monkeypox virus DNA polymerase catalytic subunit (E9L) (E9L)

The Monkeypox virus DNA polymerase catalytic subunit, encoded by the E9L gene, is a vital enzyme responsible for the replication of the Monkeypox virus (MPXV) genome (UniProt: Q8V4S9). As a member of the Orthopoxvirus genus, MPXV possesses a large, linear, double-stranded DNA genome that is replicated within the host cell's cytoplasm using virus-encoded machinery (PubMed: 35921474). The E9L protein acts as the central engine for this process, facilitating DNA-directed DNA synthesis with high fidelity. This enzyme serves as the primary target for several antiviral agents, most notably the nucleotide analogs cidofovir and its prodrug brincidofovir (CDC: Mpox Treatment Guidance). These drugs are phosphorylated by cellular kinases into active forms that compete with natural deoxyribonucleotides; once incorporated into the nascent DNA strand by the E9L polymerase, they cause premature chain termination or lead to the synthesis of defective viral DNA (PubChem: CID 60613). Clinical use of these inhibitors is primarily reserved for severe cases due to significant safety concerns, including the risk of dose-limiting nephrotoxicity and the potential for the virus to develop resistance through mutations in the E9L gene (NIH: Mpox Antiviral Research).

Other names

E9LDNA-directed DNA polymeraseMPXVgp057Monkeypox virus DNA polymeraseDNA polymerase catalytic subunit

Inhibition of viral DNA synthesis through competitive inhibition of the DNA polymerase and DNA chain termination.