Nidovirus RNA-dependent RNA polymerase-associated nucleotidyltransferase domain of non-structural protein 12 (NiRAN domain (of nsp12))

The nidovirus RdRP-associated nucleotidyltransferase domain (NiRAN domain) of non-structural protein 12 (nsp12) is an N-terminal domain present in the RNA-dependent RNA polymerase subunit of coronaviruses and other nidoviruses. This domain is essential for viral replication, performing a key enzymatic reaction: transferring nucleotidyl groups to acceptor molecules such as Nsp9 or the nascent viral RNA. The NiRAN domain is highly conserved across nidoviruses and is structurally distinct from human nucleotidyltransferases, making it an attractive target for antiviral drugs. The C-terminal portion of nsp12 contains the canonical RNA polymerase modules (fingers, palm, thumb subdomains), which, together with cofactors nsp7 and nsp8, form the replication-transcription complex required for viral RNA synthesis. Notably, the NiRAN domain’s activity is critical for both viral RNA replication and the lifecycle of the virus, as evidenced by its essential role in COVID-19 virus propagation. Drugs such as remdesivir inhibit nsp12 activity, and by extension, the NiRAN domain’s function, by incorporating as analogues during RNA synthesis and terminating chain elongation.

Other names

Nidovirus RdRP-associated nucleotidyltransferaseNiRAN domain (of nsp12)nsp12 NiRAN domainNon-structural protein 12 nucleotidyltransferase domain

Competitive inhibition or chain termination of viral RNA synthesis by incorporation of nucleotide analogs (e.g., remdesivir acts as an ATP analog). Potential interference with nucleotidyl transfer or polymerase activation.