HDAC2 is a common target of nsp5 of different CoVs. (A) Alignment of the amino acid sequences of porcine HDAC2 (GenBank accession number XP_001925353.2), human HDAC2 (GenBank accession number NP_001518.3), rat HDAC2 (GenBank accession number NP_445899.1), bovine HDAC2 (GenBank accession number NP_001068614.1), horse HDAC2 (GenBank accession number XP_023506728.1), and mouse HDAC2 (GenBank accession number NP_032255.2). The cleaved Q261 site is indicated with an pentagram. (B, C) HEK-293T cells were cotransfected with Flag-tagged human HDAC2 (hHDAC2) or porcine HDAC2 (pHDAC2) and expression plasmids encoding nsp5 of PEDV, HCoV-229E, HCoV-HKU1, MERS-CoV, SARS-CoV, SARS-CoV-2, or PDCoV. At 28 h after cotransfection, cells were collected for Western blotting with anti-Flag and anti-HA antibodies.