Table 3.

A summary of the therapies based on ACE2 used until present.

Primary drug		Condition or disease	Species	Dosage	Medication method	Results	Pros and Cons	Reference
rACE2	hrsACE2	Pulmonary hypertension	Mice (FVB/N)	1.2 mg/kg/day × 14 days	Mini-osmotic pumps	Significantly attenuated vascular remodeling and increased pulmonary SOD2 expression without measurable effects on pulmonary fibrosis.	–	Rathinasabapathy et al., 2018
	hrsACE2	COVID-19	Human	2 times/day	Intravenous injection	Significant improvement in mechanical ventilator-free Days and reduction in viral RNA load observed	–	Clinicaltrials, 2021
	hrsACE2	H5N1 infection induced acute lung injury	Mice (BALB/c)	0.1 mg/kg × 3 times	Intraperitoneal injection	Reduced acute lung injury severity and prolonged overall survival time of infected mice	–	Zou et al., 2014
	hrsACE2	ARDS	Human	0.4 mg/kg × 2 times/day ×3 days	Intravenous injection	Did not result in improvement in physiological or clinical measures of ARDS	Causes some adverse events, such as hypernatremia, pneumonia, dysphagia and rash.	Khan et al., 2017
	hrsACE2	Respiratory syncytial virus induced lung injury	Mice (C57BL/6 )	0.1 mg/kg × 3 times	Intravenous injection	Reduces the severity of lung injury.	–	Gu et al., 2016
	hrsACE2	Ang II- mediated renal oxidative stress, inflammation, and fibrosis	Mice (C57BL/6)	2 mg/kg/day × 14 days	Intraperitoneal injection	Reversed renal NADPH oxidase activation and proinflammatory changes, and attenuated tubulointerstitial fibrosis	–	Zhong et al., 2011
	hrsACE2	Ang II-induced renal fibrosis	Mice (apoE-KO)	2 mg/kg/day × 14 days	Intraperitoneal injection	Dramatically ameliorated Ang II-mediated hypertension, kidney remodeling and tubulointerstitial fibrosis	–	Chen et al., 2016a
	rACE2-Fc	Acute hypertension	Mice (BALB/c)	4 kU/kg	Intravenous injection	Significantly lowered SBP following Ang II	1. With the same dose, the peak blood concentration of rACE2-Fc was 2-fold higher than that of untagged rACE2 and could be sustained for much longer time. 2. Infusion of rACE2-Fc did not show any blood pressure-lowering effect in normotensive controls. 3. It can pass through the placental barrier and is expected to contribute to Ang II degradation during the placental passage and in the fetus. 4. Long-acting rACE2-Fc may help to address the “Ang II escape” phenomena.	Liu P et al., 2018
	rACE2-Fc	Chronic hypertension, albuminuria and multiorgan fibrosis	Mice (RenTgMK)	1 time/7 days × 42 days	Intravenous injection	1. Reduced endogenous plasma Ang II levels 2. The levels of BP and albuminuria stayed within normal ranges 3. Reduced areas of fibrosis 4. Reduced the levels of Akt and Erk phosphorylation levels		Liu P et al., 2018
	rACE2-Fc	Cardiac hypertrophy and fibrosis	Mice (C57BL/6)	1 time/7 days × 28 days	Intravenous injection	Completely prevented SBP increase, ventricular wall thickening, heart enlargement, cardiomyocyte diameter increase and interstitial and perivascular cardiac collagen deposition		Liu P et al., 2018
	ACE2 1–618-ABD	SARS-CoV-2 infection	Human kidney organoids	0.2 mg/ml	–	Markedly reduced viral replication	Prolonged duration of action and afforded more convenient dosing schedules.	Wysocki et al., 2021
	ACE2 1–618-ABD	Acute hypertension	Mice (C57BL/6)	1 mg/kg	Intraperitoneal injection	Significantly attenuated Ang II–induced hypertension
ACE2 derived peptides	23-mer (A2N)- CHIPΔTPR fusion	SARS-CoV-2 Spike-pseudotyped lentivirus infection	HEK293T cells	0.001 mg/ml	–	Reduced the infection rate of the pseudovirus by ~60%	1. Reduces the risk of immunogenicity 2. Can be readily synthesized or be efficiently packaged for delivery in a lipid nanoparticle or adeno-associated virus	Chatterjee et al., 2020
	SAP1, SAP6	SARS-CoV-2 infection	HEK293T-ACE2-GFP cells	3 mmol/L	–	Resulted in ~2-fold reduction in SARS-CoV-2 infection	–	Larue et al., 2021
	SAP1, SAP6	HCoV-NL63 infection	LLC-MK2 cells	3 mmol/L	–	Resulted in ~3-fold reduced HCoV-NL63 titers	–	Larue et al., 2021

ARDS, acute respiratory distress syndrome; NADPH, nicotinamide adenine dinucleotide phosphate; SBP, systolic blood pressure; BP, blood pressure.