Table 1.

Validation and invalidation of SARS-CoV-2 M^pro and PL^pro inhibitors

Compound	Reported SARS-CoV-2 Mpro inhibition IC50 (µM)	Reported SARS-CoV-2 PLpro inhibition IC50 (µM)	Validation results IC50 (µM)
Dieckol	IC50 = 4.5 ± 0.4 (1 mM DTT) IC50 = 2.9 ± 0.2 (no DTT) Competitive inhibitor Ki = 3.3 µM [21] SPR KD = 0.22 µM	N.A.	FRET assay: Mpro IC50 > 20 (4 mM DTT) PLpro IC50 > 20 (4 mM DTT) Flip-GFP Mpro assay: IC50 > 60 µM
PGG	SARS-CoV-2 IC50 = 3.66 ± 0.02 SARS-CoV IC50 = 6.89 ± 0.15 [22]	N. A.	FRET assay: Mpro IC50 > 20 (4 mM DTT) PLpro IC50 = 3.90 ± 1.10 (4 mM DTT) Thermal shift assay: ΔTm = 3.91 oC Flip-GFP Mpro assay: IC50 > 3 µM Flip-GFP PLpro assay: IC50 > 3 µM
Ebselen	IC50 = 3.7 ± 2.4 (4 mM DTT) IC50 > 60 (4 mM DTT) [25]	IC50 = 10.3 ± 8.9 (4 mM DTT) IC50 > 60 (4 mM DTT) [25]	Flip-GFP PLpro assay: IC50 > 30 µM
Disulfiram	IC50 = 2.1 ± 0.3 (4 mM DTT) IC50 > 60 (4 mM DTT) [25]	IC50 = 6.9 ± 4.2 (4 mM DTT) IC50 > 60 (4 mM DTT) [25]	Flip-GFP PLpro assay: IC50 > 10 µM
Carmofur	IC50 = 0.2 ± 0.1 (4 mM DTT) IC50 = 28.2 ± 9.5 (4 mM DTT) [25]	IC50 = 0.7 ± 0.1 (4 mM DTT) IC50 > 60 (4 mM DTT) [25]	Flip-GFP PLpro assay: IC50 > 50 µM
PX-12	IC50 = 0.9 ± 0.2 (4 mM DTT) IC50 > 60 (4 mM DTT) [25]	IC50 = 18.7 ± 2.6 (4 mM DTT) IC50 > 60 (4 mM DTT) [25]	Flip-GFP PLpro assay: IC50 > 50 µM
Tideglusib	IC50 = 2.1 ± 0.3 (4 mM DTT) IC50 > 60 (4 mM DTT) [25]	IC50 = 7.1 ± 1.4 (4 mM DTT) IC50 = 30.4 ± 17.1 (4 mM DTT) [25]	Flip-GFP PLpro assay: IC50 > 60 µM

N.A. not available