Table 1.

Substrate and inhibitor-binding interactions at the active site of SARS-CoV-2 Mpro. The enzyme-ligand interactions were mapped using LigPlot+ v2.2.4 [63] and based on data available in PDBsum database [62]. H-bonds (H) and non-polar interactions (NP) are also shown. The interactions that are mediated by the side chains of enzyme residues are bold, and asterisk indicates modified catalytic residue (C145A) in the enzyme-substrate complexes. The graphical representation of the interactions is shown in Figure 2.

PDB	7MGR		7MGS		7N89		7VH8		7RFW		7RFS		7SI9		7TE0		7TLL
Reference	[82]		[82]		[83]		[79]		[70]		[70]		[84]		Unpublished Study		[80]
Ligand	AVKLQ*NNE		SAVLQ*SGF		SAVLQ*SGF		nirmatrelvir		nirmatrelvir		nirmatrelvir		nirmatrelvir		nirmatrelvir		nirmatrelvir
Interaction	H	NP	H	NP	H	NP	H	NP	H	NP	H	NP	H	NP	H	NP	H	NP
S5 site		P168		P168 Q189		P168
S4 site	T190	M165 L167 R188 Q189 Q192	T190	R188 Q189 Q192	T190	R188 Q192		Q189		M165 Q189 T190		M165 Q189 T190		Q189	Q192	Q189		M165 Q189 Y190
S3 site	E166 N142	M165 Q189	E166	M165	E166	M165	E166	M165	E166	M165	E166	M165	E166	M165	E166	M165	E166	M165
S2 site		H41 M165 Q189		H41 M49 H164 M165	Q189	H41 H164 M165 D187		H41 M49 Y54 D187 R188 Q189		H41 M49 Y54 H164 M165 D187 R188 Q189		H41 M49 H164 R188 Q189		H41 M49 Q189		H41 M49 M165 Q189		H41 M49 Y54 D187 R188 Q189
S1 site	F140 G143 A145* H163 H164 E166	L141 S144 M165 H172	F140 G143 A145 * H163 H164	L141 H172	F140 G143 A145 * H163 H164 E166	L141 N142 S144 H172	F140 G143 C145 H163 H164 E166	H41 M49 Y54 L141 N142 H172 D187	G143 C145 H163	H41 M49 Y54 F140 N142 H164 M165 H172 D187 T190	C145 H163	H41 M49 F140 L141 N142 G143 H164 M165 H172 T190	F140 H163 H164 E166	H41 M49 N142 M165 H172	G143 C145 H163 H164 E166	F140 N142 G143 H172	C145 H163 H164 E166	H41 F140 L141 N142 G143 S144 H172
S1’ site	G143	T25 H41 M49	N142	T25 H41 M49		T25 H41 M49 N142
S2’ site	T26	T25	T26	T25	T26	T25
S3’ site		T24		T24		T24 S46