Table 2.

Potential treatments for coronavirus infections that target the coronavirus receptors.

Drug Family	Drug	Action Mechanism	Coronavirus Treatment	Other Uses	Ref
ANPEP inhibitors	Ubenimex	Inhibit the catalytic activity of ANPEP.	NR	Cancer treatment in study.	[132]
DPP-IV inhibitors	Gliptins	Inhibit the catalytic activity of membrane and soluble DPP-IV. Reduce glucose levels. Suppress T cell proliferation and pro-inflammatory cytokine synthesis.	Experimental models	Diabetes type 2 treatment. Anti-inflammatory drug.	[84]
ACE2 inhibitors	MLN-4760	Inhibit catalytic activity of ACE2.	Experimental models	Treatment for hypertension, cardiovascular diseases, chronic kidney disease, and diabetes mellitus.	[133]
ACE2 internalization inhibitor	Arbidol	Interacts with aromatic residues within the viral proteins and the plasma membrane. Suppresses the expression of IL-1β, IL-6, IL-12, and TNF-α.	Experimental models	Treatment for various virus including influenza, Ebola virus and hepatitis C virus.	[133,134]
ACE2 viral-binding-site blockers	NAAE (N-[2-aminoethyl]-1 aziridine ethanamine), 6-Prenylapigenin, cannabivarin and Δ8-tetrahydrocannabinolic acid-A	Block the viral docking sites of ACE2 and thus the membrane fusion with the cell membranes.	Experimental and computational models	NR	[133,135,136]
ACE2 as decoy molecules	sACE2 (GSK2586881, APN01, dimeric ACE2)	Binds to extracellular viral S proteins, thus neutralizing the virus. Ang II decreases and Ang (1–7) increases.	GSK2586881 and APN01 in Phase II clinical trial	NR	[137,138,139]
	Chimeric sACE2- IgG Fc fragment	Chimeric protein N terminus of ACE2 with a human IgG Fc fragment at the C-terminus which enhances phagocytosis and complement activation via interaction with Fc receptors.	Experimental models	NR	[140]
Decrease transmembrane ACE2	PMA (phorbol 12-myristate 13-acetate)	Enhances ADAM17 activity to increase ACE2 shedding.	In vitro study	NR	[133]
	Ionomycin	Enhances ADAM10 activity to increase ACE2 shedding.	In vitro study	NR	[133]
	Resveratrol	Reduce ACE2 expression	Phase I clinical trial	Antioxidant, anticoagulant, anti-inflammatory drug	[141]
Increase ACE2 activity	XNT (1-[(2-dimethylamino) ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthen-9-one)	Increase ACE2 activity	Experimental model	NR	[133,139]
	Diminazene aceturate	Increases ACE2 activity.	Experimental model	Anti-protozoa drugs.	[133]
	Olmesartan, losartan, telmisartan, azilsartan	ARB increases the ACE2 expression levels.	Phase III clinical trial	Used to downregulate high blood pressure.	[135,142]
	Spironolactone	Increases ACE2 mRNA in macrophages.	Clinical trials not concluded	Treatment for hyperaldosteronism and diuretic drug.	[135,143]
	Apelin-13	Substrate of ACE2.	As hypothesis	Peptide used to treat cardiovascular diseases.	[135,144]