Enterovirus non-structural protein 2C (2C)

Enterovirus non-structural protein 2C is a highly conserved, multifunctional enzyme essential for the replication cycle of viruses within the Enterovirus genus, including poliovirus, enterovirus A71, and coxsackievirus [1, 3, 9]. Belonging to the AAA+ ATPase superfamily and Helicase Superfamily 3 (SF3), 2C coordinates critical processes such as viral RNA synthesis, the remodeling of host membranes into replication organelles, and the encapsidation of the viral genome [3, 11]. Because it is among the most conserved proteins across diverse enterovirus species, it is a primary target for the development of broad-spectrum, pan-enteroviral therapeutics [1, 9]. Several repurposed drugs, such as the (S)-enantiomer of fluoxetine and the anesthetic dibucaine, have been identified as 2C inhibitors that act by binding to allosteric sites to disrupt the protein's enzymatic activity or its ability to form functional hexamers [2, 5, 8]. However, therapeutic challenges remain, particularly the rapid emergence of escape mutants and the fact that many current inhibitors show activity against only specific species (e.g., EV-B and EV-D) rather than the entire genus [2, 4, 7].

Other names

Enterovirus 2C AAA+ ATPaseP2C2C protein2C ATPase2C helicaseNon-structural protein 2C

Inhibition of ATP hydrolysis through allosteric binding, disruption of hexameric oligomerization, or interference with RNA binding and membrane association.