Monkeypox virus DNA polymerase (F8L) (F8L)

The Monkeypox virus DNA polymerase (F8L) is the catalytic subunit of the viral DNA replication machinery, essential for the synthesis and maintenance of the double-stranded DNA genome. It belongs to the B-family of DNA polymerases and works in conjunction with processivity factors (A22R and E4R) to ensure efficient viral replication within the host cell's cytoplasm. In the context of the 2022 Mpox outbreak, this enzyme became a primary focus for drug discovery, with researchers utilizing modeled structures (e.g., AlphaFold or homology models) to identify potential inhibitors before experimental structures were available. The DNA polymerase is the primary target for the antiviral drugs Cidofovir and its prodrug Brincidofovir, which act as nucleoside analogs that compete with natural dNTPs, leading to chain termination and inhibition of viral DNA synthesis. Resistance to these drugs can occur through mutations in the F8L gene, highlighting the need for continued monitoring and the development of novel therapeutic strategies. Safety concerns associated with targeting this enzyme primarily involve the nephrotoxicity of certain inhibitors like Cidofovir, which requires careful clinical management.

Other names

F8LDNA polymerase catalytic subunitE9L homologMPXVgp054DNA-directed DNA polymerase

DNA polymerase inhibition; competitive inhibition of dNTP incorporation; DNA chain termination