Table 1.

Orthosteric and allosteric binding sites for the therapeutically relevant protein targets as derived from the literature search.

Protein	Source a	Function	Reference Protein	PDB Id	Site	Ligand c	Ref.
3CL-PRO	See Table 2	protease	---b	---b	orthosteric	3WL	[15,16]
N-Protein	6M3M 6VYO	Nucleocapsid protein	HCoV-OC43 N-NTD	4LMC	orthosteric	C5P	[17]
				4LM9		5GP
				4LM7		U5P
				4LI4		AMP
				4KXJ		P34
Nsp3	6W02	ADP ribose phosphatase	---	---	orthosteric	ADP	*** d
Nsp6	DN	Membrane-spanning protein	No experimental information apart from mutants analysis	---	allosteric	K22	[18]
Nsp9	6W4B	Replicase	Coronavirus NSP9	1QZ8	orthosteric	SO4	[19]
			Type 2 rhinovirus 3C protease	1CQQ	orthosteric	AG7	[20]
Nsp12	7BV2	RNA-dependent RNA polymerase (RdRp)	---	---	orthosteric	F86	***
			Hepatitis C RdRp	2BRL	allosteric1 (thumb)	POO	[21]
			Hepatitis C NS5B polymerase	2HAI	alllosteric2 (thumb)	PFI	[22]
			Hepatitis C NS5 polymerase	3HHK	allosteric3 (palm)	77Z	[23]
Nsp13	HM	Helicase	RNA-Dependent ATPase Upf1	2XZL	orthosteric	ADP-ALF	[24]
			Hepatitis C virus NS3 protein	4B75	Allosteric	4VA	[25]
Nsp14	HM	Methyltransferase	SARS-CoV	5C8S	orthosteric	SAH, G3A	[26]
Nsp15	6W01	Endoribonuclease	SARS-CoV	2H85	orthosteric	U3M	[27]
Nsp16	6WKS 6W4H	Methyltransferase	---	---	orthosteric	SAM, GTA	***
PL-pro	6W9C	Papain-like protease	SARS-CoV	3E9S	orthosteric	TTT	***
Spike	Xray with ACE2	Viral entry glycoprotein	---	---	Protein–protein interaction	YMZ	[28,29,30,31,32,33,34,35,36]

^a For resolved proteins, the corresponding PDB Id is reported, while for modelled structures, HM and DN mean homology modeling and de novo modeling, respectively. ^b --- means that the binding site was directly identified from the resolved protein SARS-CoV-2 structure. ^c The IUPAC name of the probe ligands can be found in the Abbreviations. ^d *** indicates that the resolved SARS-CoV-2 protein structures are available in PDB, while the corresponding paper is still unpublished.