TABLE 1.

Summary of reported drug repurposing attempts against SARS-CoV-2 PLro.

Name	Chemical Structure(s)	Current Clinical Use(s)	Primary assay	Orthogonal Assay(s)	Counter Screen(s)	Comments	References(s)
Tanshinone and derivatives
Sodium Tanshinone IIA Sulfonate		Hypertension, Myocardial infarction, coronary artery disease	Z-ALKGG-AMC	SPR (KD of 61 µM)	No	- Dosage used substantially higher than the clinic	Xu et al. (2021)
			ISG15-FITC (FP assay)			- KD measured of 61 µM
Cryptotanshinone		Immunosuppressant, anticancer treatment, vasodilator	Plaque reduction assay	No	No	- Not tested against full Ub substrate	Lim et al. (2021); Zhao et al. (2021)
						- No assay to measure direct binding
						- More potent in cells than in biochemical assay, suggests cytotoxicity
Tanshinone I		Oncolytic treatment, chemopreventative agent	Abz-FTLKGGAPTKVT-DNP (FRET)	No	No	- Not tested against full Ub substrate
Tanshinone IIA		Oncolytic drug, vasodilator, treatment of stroke				- No conclusive follow up assays	Lim et al. (2021)
						- Known inducer of apoptosis Fang et al. (2021)
HCV Drugs
Asunaprevir		Hepatitis C Virus (HCV), NS3/4 serine protease inhibitor	Z-RLRGG-AMC	No	No	- Extremely low starting IC50 (54 µM)	Anson et al. (2020)
						- Optimised for a very different protease
Simeprevir			Phenotypic screen	No	No	- Entirely phenotypic screen	Anson et al., (2020); Gammeltoft et al. (2021)
						- Often a sharp decline in cell viability, indicating just lagging in dying of virus
Vaniprevir/Simeprevir			Z-RLRGG-AMC	No	No	- Follow up assays solely synergistic phenotypic screens
Others
Famotidine		H2AR agonist – stomach and intestinal ulcers	Z-ALKGG-AMC	No	No	- Dosing used far exceeds its intended indication	Wu et al., 2020a; Kandeel et al., 2020)
			ISG15-FITC (FP assay)			- Refuted in a recent in vitro study Loffredo et al. (2021)
Ebselen		Meniere’s disease and hearing loss	Ub-AMC	No	No	- Se is highly reactive against cysteines	Sargsyan et al. (2020); Weglarz-Tomczak et al. (2021)
						- Only showed inhibitory activity after a prolonged incubation
Disulfiram		Anti-cancer agent	Abz- FTLKGGAPTKVT-DNP (FRET)	No	No	- Likely nonspecific to all zinc finger containing proteins (including other DUBs)	Sargsyan et al. (2020)
Acriflavine		Nil	Z-RLRGG-AMC	No	No	- DNA intercalating agent	Napolitano et al. (2022)
						- Biological targets are unclear
Repurposed “lead” compounds
GRL-0617		Nil	Varies (see Table 2)	Yes	Yes	- Repurposed early stage compound optimised for SARS-CoV	Shin et al. (2020) and see Table 2
5c		Nil	Ub-Rh110	Yes	Yes		Klemm et al. (2020); Shan et al. (2021)
3k		Nil	Ub-Rh110	Yes	Yes		Calleja et al. in this issue