Fig. 5

Sequence comparison of Mac-1 and its capacity to bind ADPr. (a) Comparison of mutant Mac-1 sequence from Pakistani SARS-CoV-2 isolates (EPI_ISL_1406395, QQH15880, and QQL13872) to that of Mac-1 sequence from reference Wuhan strain of SARS-CoV-2 (PDB entry: 6W02), SARS-CoV (PDB entry: 2FAV), MERS-CoV (PDB entry: 5HOL), Bat-SL-CoV (AVP78030.1), and Bat-RatG13 (QHR63299.1). Secondary structure elements are shown in red at the top of the alignment. In alignment, amino acid substitutions within Mac-1 of Pakistani SARS-CoV-2 isolate is highlighted in blue with an asterisk (*) symbol. The amino acid residues of reference SARS-CoV-2 (PDB entry: 6W02) and its Mac-1 Mutant versions (M265I, G307C and L357I) that form H-bond with the ADP-ribose (ADPr) are highlighted as pink and green, respectively. ADPr interacting residues of SARS-CoV(PDB entry: 2FAV) and MERS-CoV (PDB entry: 5HOL) are highlighted in yellow and orange, respectively and were adopted from previously published work [15].(b-e) The LigPlot diagram depicting the 2D interaction pattern of wild-type (PDB entry: 6W02) and Mutant (M265I, G307C and L357I) Mac-1 with ADPr. Legend: thick red lines, ADP ribose ligand; thin black lines, Mac-1 amino acid residue; semi circles with radiating lines represent residues involved in hydrophobic interactions. The Mac-1 residues that form an H-bond with ADPr are represented as green dashed lines in panel b-e