Foot-and-mouth disease virus RNA-dependent RNA polymerase (FMDV 3Dpol)

Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (3Dpol) is the core catalytic enzyme responsible for the replication and transcription of the viral RNA genome [NIH, 2020]. As a member of the Picornaviridae family, FMDV relies on 3Dpol to synthesize both negative-strand intermediates and new positive-strand genomic RNA, as well as to catalyze the uridylylation of the VPg primer protein [PLoS ONE, 2023]. The enzyme adopts a conserved right-hand architecture consisting of fingers, palm, and thumb subdomains, which coordinate the binding of the RNA template and nucleotide triphosphates [NIH, 2022]. Because RNA-dependent RNA polymerases are absent in mammalian hosts, 3Dpol represents a highly specific and attractive therapeutic target for antiviral intervention [PLoS ONE, 2010]. Various inhibitors, including nucleoside analogs like ribavirin and non-nucleoside allosteric inhibitors, have been developed to disrupt its activity, thereby preventing viral progeny production and controlling outbreaks in livestock [MDPI, 2024].

Other names

3D polymerase3DpolFMDV 3D proteinP3DRNA-directed RNA polymerase 3D-POL

Inhibition of viral RNA synthesis by acting as a nucleoside analog (inducing lethal mutagenesis or chain termination) or as a non-competitive inhibitor binding to allosteric pockets [PLoS ONE, 2010; NIH, 2022].