RNA-dependent RNA polymerase (RdRp) in the Enterovirus genus of positive-sense single-stranded RNA [(+)ssRNA] viruses, within the family Picornaviridae
This group contains the RdRp of RNA viruses belonging to the Enterovirus genus within the family Picornaviridae, order Picornavirales. Enteroviruses have small, non-enveloped (+)ssRNA genomes, and replicate within the gastrointestinal tract or other mucosal surfaces. The genus Enterovirus has been divided into 15 species based on genetic divergence (EV A-L and Rhinovirus A-C), and its major members include poliovirus, coxsackievirus and rhinovirus. More than 100 enterovirus types have been associated with several human diseases, all of which are classified into four species (Enterovirus A, Enterovirus B, Enterovirus C, and Enterovirus D). RdRps are multi-domain proteins that play a pivotal role in enterovirus replication. RdRps catalyze RNA template-dependent formation of phosphodiester bonds between ribonucleotides in the presence of divalent metal ions. The initiation of synthesis occurs at the 3'-end of the template in a VPg-dependent manner, and proceeds in the direction of 5'-3'. The active sites of RdRps are highly conserved in different species of enteroviruses. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.