PROSITE documentation PDOC51947
Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain profile


Positive-stranded RNA (+RNA) viruses that belong to the order Nidovirales infect a wide range of vertebrates (families Arteriviridae and Coronaviridae) or invertebrates (Mesoniviridae and Roniviridae). Examples of nidoviruses with high economic and societal impact are the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) and the zoonotic coronaviruses (CoVs) causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Covid-19 (SARS-CoV-2) in humans.

In all nidoviruses, at least two-thirds of the capacity of the polycistronic genome is occupied by the two large open reading frames (ORFs; 1a and 1b) that together constitute the replicase gene. The two polyproteins produced, pp1a (ORF1a-encoded) and pp1ab (ORF1a/ORF1b-encoded), are processed to a dozen or more proteins by the virus' main protease (3CLpro, encoded in ORF1a) (see <PDOC51442>) with possible involvement of other protease(s). These and other proteins form a membrane-bound replication-transcription complex (RTC) that invariably includes two key ORF1b-encoded subunits: the RNA-dependent RNA polymerase (RdRp) and a superfamily 1 helicase domain (HEL1) (see <PDOC51657>), which is fused with a multinuclear Zn-binding domain (ZBD) (see <PDOC51652>). The RNA-dependent RNA polymerase (RdRp) domain of nidoviruses resides in a cleavage product of the replicase polyprotein named non-structural protein (nsp) 12 in coronaviruses and nsp9 in arteriviruses. In all nidoviruses, the C-terminal RdRp domain is linked to a conserved N-terminal domain, which has been coined NiRAN (nidovirus RdRp-associated nucleotidyl transferase). The NiRAN domain has an essential nucleotidylation activity and its potential functions in nidovirus replication may include RNA ligation, protein-primed RNA synthesis, and the guanylyl-transferase function that is necessary for mRNA capping [1,2,3,4,5].

The NiRAN domain is characterized by an α + β fold composed of eight α helices and a five stranded β-sheet (see <PDB:7BTF>). In addition, an N-terminal β-hairpin interacts with the palm subdomain of the RdRp domain [5,6].

The profile we developed covers the entire Nidovirus NiRAN domain.

Last update:

October 2020 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

NIRAN, PS51947; Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain profile  (MATRIX)


1AuthorsLehmann K.C. Gulyaeva A. Zevenhoven-Dobbe J.C. Janssen G.M.C. Ruben M. Overkleeft H.S. van Veelen P.A. Samborskiy D.V. Kravchenko A.A. Leontovich A.M. Sidorov I.A. Snijder E.J. Posthuma C.C. Gorbalenya A.E.
TitleDiscovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses.
SourceNucleic. Acids. Res. 43:8416-8434(2015).
PubMed ID26304538

2AuthorsPosthuma C.C. Te Velthuis A.J.W. Snijder E.J.
TitleNidovirus RNA polymerases: Complex enzymes handling exceptional RNA genomes.
SourceVirus. Res. 234:58-73(2017).
PubMed ID28174054

3AuthorsKirchdoerfer R.N. Ward A.B.
TitleStructure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors.
SourceNat. Commun. 10:2342-2342(2019).
PubMed ID31138817

4AuthorsSaberi A. Gulyaeva A.A. Brubacher J.L. Newmark P.A. Gorbalenya A.E.
TitleA planarian nidovirus expands the limits of RNA genome size.
SourcePLoS Pathog. 14:E1007314-E1007314(2018).
PubMed ID30383829

5AuthorsRomano M. Ruggiero A. Squeglia F. Maga G. Berisio R.
TitleA Structural View of SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping.
SourceCells 9:0-0(2020).
PubMed ID32443810

6AuthorsGao Y. Yan L. Huang Y. Liu F. Zhao Y. Cao L. Wang T. Sun Q. Ming Z. Zhang L. Ge J. Zheng L. Zhang Y. Wang H. Zhu Y. Zhu C. Hu T. Hua T. Zhang B. Yang X. Li J. Yang H. Liu Z. Xu W. Guddat L.W. Wang Q. Lou Z. Rao Z.
TitleStructure of the RNA-dependent RNA polymerase from COVID-19 virus.
SourceScience 368:779-782(2020).
PubMed ID32277040

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