Enterovirus A71 RNA-dependent RNA polymerase (3Dpol) (3Dpol)

Enterovirus A71 RNA-dependent RNA polymerase (3Dpol) is the core catalytic enzyme responsible for the replication and transcription of the viral positive-sense single-stranded RNA genome [1, 5]. It functions by synthesizing a negative-strand RNA intermediate from the genomic template, which then serves as a template for the production of progeny positive-strand RNAs [5, 12]. Additionally, 3Dpol catalyzes the uridylylation of the viral protein VPg, a critical step that provides the primer necessary for initiating RNA synthesis [1, 12]. Beyond its enzymatic role, 3Dpol interacts with numerous host factors, such as ribosomal proteins and splicing factors, to hijack the cellular translation machinery and suppress host immune responses [1, 2, 12]. EV-A71 is a primary cause of hand, foot, and mouth disease (HFMD) and can lead to severe, life-threatening neurological conditions like brainstem encephalitis and acute flaccid paralysis [5, 11, 13]. Because 3Dpol is essential for viral survival and lacks a direct human homolog, it is considered a premier target for the development of direct-acting antivirals [6, 7, 11]. Therapeutic agents targeting this enzyme include nucleoside analogs that induce premature chain termination and non-nucleoside inhibitors that allosterically interfere with the polymerase's elongation activity [7, 10, 11]. Research into 3Dpol inhibitors is ongoing, with several compounds demonstrating potent activity in preclinical models, although the rapid emergence of resistant mutations remains a significant therapeutic challenge [7, 11].

Other names

3D polymeraseEV71 3DpolRdRp3D proteinEnterovirus A71 3D polymeraseEnterovirus 71 RNA-dependent RNA polymerase

Inhibition of viral RNA synthesis through chain termination or allosteric inhibition of the polymerase elongation activity.