Coronaviruses (CoVs) are enveloped positive-strand RNA viruses that infect many species, including humans, other mammals, and birds. After infection, the host may develop respiratory, bowel, liver, and neurological diseases. Coronaviruses are divided into four genera: αcoronavirus, βcoronavirus, γcoronavirus, and Deltacoronavirus. SARS, SARS-CoV-2, BatCoV RaTG13 and Bat-SARS-like coronavirus (BATSL-CoVZXC21 and BAT-SL-CoVZC45) belong to the Sarbecovirus subgenus of βcoronavirus [E1].

The CoV replicase gene encodes two overlapping polyproteins, termed pp1a and pp1ab, which mediate viral replication and transcription. The polypeptides pp1a and pp1ab are processed by the action of a main protease (Nsp5) (see <PDOC51442>) and of one or two papain-like proteases (PLpro) (see <PDOC51124>) found in Nsp3 into non-structural proteins (Nsps) to form the replication/ transcription complex (RTC). Among these, Nsp3 is a glycosylated, multidomain, integral membrane protein. Nsp3 plays many roles in the viral life cycle. It can act as a scaffold protein to interact with itself and to bind other viral Nsps or host proteins. In particular, Nsp3 is essential for RTC formation. Nsp3 comprises various domains of functional and structural importance for virus replication, the organization of which differs between CoV genera, due to duplication or absence of some domains [1]. Two ubiquitin-like domains (see <PDOC00271>), Ubl1 and Ubl2 (Nsp3a and the N-terminal domain of Nsp3d), exist within Nsp3 of all CoVs. The known functional roles of Nsp3a Ubl in CoVs are related to single-stranded (ssRNA) binding and interacting with the nucleocapsid (N) protein (see <PDOC51928>) [2,3]. Nsp3d Ubl is immediately adjacent to the N-terminus of the PLpro (or PL2Pro) domain in CoV polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection [4,5,6,7].

In addition to the four β-strands and two α-helices that are common to ubiquitin-like folds, the Nsp3a Ubl domain contains two short helices (see <PDB:2IDY>) [2,3]. The Nsp3d Ubl domain comprises five β-strands, one α-helix, and one 3(10)-helix (see <PDB:4P16>) [4,5,7].

The profiles we developed cover the entire CoV Nsp3a and Nsp3d Ubl domains.