Table 1.

Early-stage noncovalent inhibitors against SARS-CoV-2 PLpro^a

Inhibitor	Name in study	Potency in biochemical assays (IC50)	Potency in cellular assays (EC50)	Discovery method	Targeted subsites	Refs
GRL-0617	GRL-0617	1.5 μM	21 μM (Vero E6)	HTS	S3, S4	[20]
Tanshinone IIA	Tanshinone IIA sulfonate sodium	1.65 μM	Not tested	HTS	S3, S4	[34]
C1	DY2-97	~100 μM	Not tested	Derivative of GRL-0617	S3, S4	[37]
C2	ZN-3-61	>>10 μM	Not tested	Derivative of GRL-0617	S3, S4	[37]
C3	Compound 2	5.1 μM	No inhibition (Vero E6)	Derivative of GRL-0617	S3, S4	[26]
C4	Compound 12	2.69 μM	Not tested	Derivative of GRL-0617	S3, S4	[33]
C5	Compound 19	0.44 μM	0.18 μM (HeLa-hACE2)	Derivative of GRL-0617	S3, S4	[33]
C6	XR8-24	0.56 μM	1.2 μM (Vero E6)	Derivative of GRL-0617	S3, S4, BL2 groove	[37]
C7	F0213	7.4 μM	4.5 μM (Vero E6)	HTS	S3, S4	[46]
C8	Jun9-72-2	0.67 μM	6.62 μM (Vero E6); 7.90 μM (Caco2-hACE2)	HTS	S3, S4	[47]
C9	Jun9-75-4	0.62 μM	7.88 μM (Vero E6); 12.48 μM (Caco2-hACE2)	HTS	S3, S4	[47]
C10	Compound 56	1.42 μM	Not tested	VS	S3, S4	[51]
C11	Compound 2	0.6 μM	Not tested	VS	S3, S4	[52]
C12	Compound 7	0.085 μM	Not tested	VS	S3, S4	[53,54]
C13	Compound 13	0.063 μM	Not tested	VS	S3, S4	[53,54]

^aAbbreviations: BL2, blocking loop 2; hACE2, human angiotensin-converting enzyme 2.