Nidovirus RNA-dependent RNA polymerase-associated nucleotidyltransferase domain (NiRAN)

The Nidovirus RNA-dependent RNA polymerase-associated nucleotidyltransferase (NiRAN) domain is a highly conserved enzymatic component found in the replication-transcription complex of viruses within the order Nidovirales, such as SARS-CoV-2 (Lehmann et al., 2015, Nucleic Acids Res). It is located at the N-terminus of the non-structural protein 12 (nsp12), which also houses the primary RNA-dependent RNA polymerase (RdRp) domain (Yan et al., 2021, Cell). The NiRAN domain exhibits nucleotidyltransferase activity, which is essential for the initiation of viral RNA synthesis and the formation of the 5' cap structure on viral mRNA (Shannon et al., 2022, Nat Commun). Specifically, it functions as a guanylyltransferase, transferring a GTP molecule to the 5' end of the nascent RNA strand. This domain is critical for viral viability, as mutations in its catalytic residues typically abolish viral replication. Because the NiRAN domain has no close structural homologs in human cells, it represents a high-value target for the development of specific antiviral therapies (Park et al., 2022, J Virol). Compounds like suramin have been identified as potent inhibitors of the NiRAN domain, effectively blocking the replication of various coronaviruses in vitro (Yin et al., 2021, Nat Struct Mol Biol). Targeting this domain offers a strategy for broad-spectrum antiviral intervention against emerging nidoviruses.

Other names

NiRAN domainnsp12 NiRAN domainNucleotidyltransferase domain of nsp12Nidovirus-specific RdRp-associated nucleotidyltransferase

Inhibition of nucleotidyltransferase activity to prevent viral RNA synthesis initiation and mRNA capping.