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 nonstructural proteins (Nsps) by the virus’ main protease (3CLpro, encoded in ORF1a) (see <PDOC51442>) with possible involvement of other protease(s). Among the Nsps found in Nidovirales, nonstructural protein 15 (nsp15) from coronaviruses and Nsp11 from arteriviruses participate in the viral replication process and in the evasion of the host immune system. They contain in their C-terminal region a conserved endoribonuclease domain called nidoviral uridylate-specific endoribonuclease (NendoU) with cleavage specificity for single- and double-stranded RNA 5' of uridine nucleotides to produce a 2'-3'-cyclic phosphate end product. The NendoU domain is not conserved in those nidovirus branches that replicate in invertebrate hosts (Mesoniviridae, Roniviridae), suggesting specific roles in vertebrate hosts [1,2,3,4,5,6,7,8].

The NendoU domain packs into two β-sheets which constitute the catalytic-site cleft located at one side of the domain. A group of small α-helices packed at the other side of the domain face the concave surface of the β-sheets. The active site, located in the shallow groove between the two β-sheets, carries the catalytic triad made of two histidines and a lysine [4,5,6,7,8].

The profile we developed covers the entire NendoU domain.