PROSITE documentation PDOC51966

Coronavirus (CoV) 3a-like viroporin transmembrane (TM) and cytosolic (CD) domains profiles

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. The ideal hosts of αCoV and βCoV are mammals, and γCoV primarily infects birds, while DeltaCoV has been identified in both mammals and birds. SARS, SARS-CoV-2, BatCoV RaTG13 and Bat-SARS-like coronavirus (BATSL-CoVZXC21 and BAT-SL-CoVZC45) belong to the Sarbecovirus subgenus of βCoV [E1].

All coronaviruses have a similar genomic structure. At the 5' end, two-thirds of the genome comprises two large open reading frames (ORFs) (ORF1a and ORF1b) encoding the coronavirus replicase, which is highly conserved among genera. At the 3' end, the genome encodes four structural proteins (S, E, M and N) and a variable number of accessory proteins. Accessory proteins play an important role in virus–host interactions, especially in antagonizing or regulating host immunity and virus adaptation to the host. There are large variations in the number of accessory proteins (1–10) among coronaviruses. The number of accessory proteins of the αCoVs is relatively lower, between 1 and 5, while βCoVs have 3–5 accessory proteins, except for SARS-CoV and SARS-CoV-2, which possess the largest number of accessory proteins among all coronaviruses (10 and 9, respectively). 3a-like accessory proteins are found in multiple αCoV and βCoV lineages that infect bats and humans. They are transmembrane proteins of the viroporin family that form ion channels in the host membrane and have been implicated in inducing apoptosis, pathogenicity, and virus release. The induction of cytokine storms in COVID-19 patients might be linked to ORF3a mediated activation of inflammasome. 3a-like viroporins contain a transmembrane domain (TM) and a cytosolic domain (CD) [1,2,3,4,5,6,7].

The 3a-like viroporin TM domain is composed of three helices and the CD domain of two anti-parallel β-sheets forming a β-sandwich (see <PDB:6XDC>). The 3a-like viroporin forms a dimer and the six transmembrane helices of the dimer form an ion channel with polar/charged residues in the interior of the channel capable of conducting cations [3].

The profiles we developed cover respectively the entire CoV 3a-like viroporin TM and CD domains.