Conserved structural and sequence features of ExoN and 2′-O-MTase domains in non-mammalian arteriviruses. (A) The first two images in the panel display the representative AF3-predicted 3D structure and the corresponding schematic topology of the ExoN domain from non-mammalian arteriviruses. The structural superpositions on the right show the alignment of the arterivirus ExoN domain with the DnaQ exonuclease (PDB ID: 8H18), with a zoomed-in view (far right) highlighting the alignment of the DEDDH catalytic residues. (B) The first two illustrations in the panel depict the representative AF3-predicted 3D structure and the corresponding schematic topology of the 2′-O-MTase domain from non-mammalian arteriviruses. The structural superpositions on the right illustrate the alignment of the 2′-O-MTase domains from arteriviruses and coronaviruses (NSP16 2′-O-MTase), with a zoomed-in inset (far right) emphasizing the catalytic K-D-K-E tetrad. (C) Representative 2'-O-MTase (PDB: ID 2XYQ) from coronavirus, and AF3-predicted 3D structure of 2′-O-MTases from other Nidovirales. (D) Representative MSA of 2′-O-MTases across all Nidovirales, highlighting key conserved motifs for S-adenosyl methionine (SAM) binding, substrate binding, and the K-D-K-E catalytic tetrad.