This domain covers the N-terminal region of the coronavirus RNA-directed RNA Polymerase which corresponds to the nonstructural protein 12 (NSP12) produced by cleavage of ORF1b. NSP12 contains a polymerase domain that assumes a structure resembling a cupped 'right hand', similar to other polymerases, containing a fingers domain, a palm domain and a thumb domain. Coronavirus NSP12 also contains a nidovirus-unique N-terminal extension (nidovirus RdRp-associated nucleotidyltransferase (NiRAN) that possesses a kinase-like fold allowing the binding of NSP12 to NSP7 and NSP8. NSP12 possesses some minimal activity on its own, but the addition of the NSP7 and NSP8 co-factors greatly stimulates polymerase activity. This domain represents the N-terminal region of the coronavirus RNA-directed RNA Polymerase, which includes the NiRAN and interface domains. The function of the NiRAN domain is not clear and its target is yet unknown, but it has enzymatic activity that is essential for viral propagation. Structure from SARS-CoV-2 revealed that this domain binds ADP-Mg+2, which may constitute a new pocket for anti-viral treatment development.
Jiyao W et al.(2023). "The conserved domain database in 2023.",