3.4.17.23	analysis	ACE2-based biosensor designed to detect both SARS-CoV-2 S1 mutations and neutralizing antibodies. In binding mode, the biosensor works by detecting binding of the spike protein to an immobilized ACE2 receptor and is able to detect S1 proteins of the alpha (500 pg/ml) and beta variants (10 ng/ml), as well as wild-type S1 (10 ng/ml), of SARSCoV-2 and it distinguishes wild-type SARS-CoV-2 S1 from the S1 alpha and beta variants via color differences. A modification to the protocol enables the ACE2-based biosensor to operate in blocking mode to detect neutralizing antibodies in serum samples from COVID-19 patients	764335	
3.4.17.23	analysis	analysis of the interaction between ACE2 and SARS-CoV-2 spike protein using a surface plasmon resonance-based assay that reduces the heterogeneity introduced from multivalent binding interactions to enable the determination of the kinetic rate constants for multivalent binding interactions. Controlling the sensor surface heterogeneity enables the deconvolution of the avidity-induced affinity enhancement for the SARS-CoV-2 spike protein and ACE2 interaction	763883	
3.4.17.23	analysis	application of CEBIT, i.e. Condensate-aided Enrichment of Biomolecular Interactions in Test tubes for high-throughput screening of drugs to inhibit the interaction between the receptor-binding domain of SARS-CoV-2 spike protein and its obligate receptor ACE2	764799	
3.4.17.23	analysis	easy-to-use method for determining ACE2 activity in brain tissue and cerebrospinal fluid, based on a quenched fluorescent substrate and presence and absence of inhibitor DX600. The method can be adapted for other tissues, plasma, cell extracts, and cell culture supernatants	754629	
3.4.17.23	analysis	mass spectrometric assay for angiotensin-converting enzyme 2 using angiotensin II as substrate will have applications in drug screening, antagonist development, and clinical investigations	668895	
3.4.17.23	analysis	method for measurement of ACE2 activity in biological fluids, using hydrolysis of an intramolecularly quenched fluorogenic ACE2 substrate, in the absence or presence of the ACE2 inhibitors MLN-4760 or DX600. ACE2 detection ranges from 1.56 to 50 ng/ml. MLN-4760 potently inhibits the activity of both human and mouse ACE2, DX600 (linear form) only effectively blocks human ACE2 activity in this assay. In biological samples of human and mouse urine, cell culture medium from mouse proximal tubular cells, and mouse plasma, the mean intra- and interassay coefficients of variation of the assay range from 1.43 to 4.39 %, and from 7.01 to 13.17 %, respectively	754628	
3.4.17.23	analysis	method for measurement of ACE2 activity in biological fluids, using hydrolysis of an intramolecularly quenched fluorogenic ACE2 substrate, in the absence or presence of the ACE2 inhibitors MLN-4760 or DX600. ACE2 detection ranges from 1.56 to 50 ng/ml. MLN-4760 potently inhibits the activity of both human and mouse ACE2, DX600 (linear form) only effectively blocks human ACE2 activity in this assay. In biological samples of human and mouse urine, cell culture medium from mouse proximal tubular cells, and mouse plasma, the mean intra- and interassay coefficients of variation of the assay range from 1.43 to 4.39%, and from 7.01 to 13.17%, respectively	754628	
3.4.17.23	diagnostics	ACE2 levels is a putative early biomarker of SARS-CoV-2 infection severity	763771	
3.4.17.23	drug development	a super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection	763700	
3.4.17.23	medicine	17-beta-estradiol may reduce SARS-CoV-2 infection of lung epithelial cells	764554	
3.4.17.23	medicine	ACE-2 protects against lung fibrogenesis by limiting the local accumulation of the profibrotic peptide angiotensin II	677486	
3.4.17.23	medicine	ACE2 activators are a reliable approach which could lead to the development of a novel class of antihypertensive and cardioprotective drugs	693702	
3.4.17.23	medicine	ACE2 is a functional receptor for the causative agent of severe acute repiratory syndrome, the SARS coronavirus, ACE2 also plays a role in the development of liver fibrosis and subsequent cirrhosis	678102	
3.4.17.23	medicine	ACE2 is a key factor for protection from ARDS/acute lung injury and it functions as a critical SARS receptor in vivo, recombinant ACE2 protein might not only be a treatment to block spreading of SARS but also to protect SARS patients from developing lung failure	679135	
3.4.17.23	medicine	ACE2 may be a target for therapeutic interventions that aim to reduce albuminuria and glomerular injury	680388	
3.4.17.23	medicine	ACE2 offers a new target for the treatment of hypertension and other cardiovascular diseases	691838	
3.4.17.23	medicine	ACE2 protects against acute lung injury in several animal models of acute respiratory distress syndrome. Increasing ACE2 activity might be a novel approach for the treatment of acute lung failure in several diseases	668354	
3.4.17.23	medicine	ACE2 protects murine lungs from acute respiratory distress syndrome	679703	
3.4.17.23	medicine	ACE2-overexpressing A549 cell-derived microparticles are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered microparticles dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages. Then, ACE2-overexpressing A549 cell-derived microparticles increase the endosomal pH but decrease the lysosomal pH in alveolar macrophages, thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for degradation. In addition, ACE2-overexpressing A549 cell-derived microparticles also inhibit the proinflammatory phenotype of alveolar macrophages, leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side effects	764444	
3.4.17.23	medicine	administration of ACE2 activators may be a valid strategy for antihypertensive therapy	692586	
3.4.17.23	medicine	among 226000 SARSCoV-2 sequences, 1573 missense mutations are found in the spike gene, and 226 of them were within the receptor-binding domain region that directly interacts with human ACE2. Modeling shows that most of the 74 missense mutations in the receptor-binding domain region of the interaction interface have little impact on spike binding to ACE2, whereas several within the spike receptor-binding domain increase the binding affinity toward human ACE2 thus making the virus likely more contagious	764531	
3.4.17.23	medicine	analysis of variations in SARS-CoV-2 spike protein and hACE2 receptor protein and their interaction in the infection scale. Interactions of hACE2 variants with SARS-CoV-2 variants are very strong for G726R-G476S, R768W-V367F, Y252N-V483A, Y252N-V367F, G726R-V367F, N720D-V367F and N720DF486L, and weak for P263S-S383C, RBD-H378R, G726R-A348T	765112	
3.4.17.23	medicine	angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2 of certain species can be utilized by SARS-CoV-2. SARS-CoV-2 tends to utilize ACE2 of various mammals, except murines, and some birds, such as pigeon. This prediction may help to screen the intermediate hosts of SARS-CoV-2. SARS-CoV-2 has a high genetic relationship with a bat coronavirus (BatCoV RaTG13) with a 96% genomic nucleotide sequence identity. The close phylogenetic relationship to Bat RaTG13 provides evidence for a bat origin of SARS-CoV-2. Direct transmission of the virus from bats to humans is unlikely due to the lack of direct contact between bats and humans (in Wuhan, China). There are probably intermediate hosts transmitting SARS-CoV-2 to humans. Combined phylogenetic analysis and critical site marking is used to predict the utilizing capability of ACE2 from different animal species by SARS-CoV-2. It is confirmed that pangolin (Manis javanica), cat (Felis catus), cow (Bos taurus), buffalo (Bubalus bubalis), goat (Capra hircus), sheep (Ovis aries) and pigeon (Columba livia) ACE2 might be utilized by SARS-CoV-2, indicating potential interspecies transmission of the virus from bats to these animals and among these animals	754646	
3.4.17.23	medicine	angiotensin-converting enzyme 2 (ACE2) fused to the Fc portion of immunoglobulin neutralizes SARS-CoV-2 in vitro. Provision of soluble recombinant human ACE2 protein can be beneficial as a novel biologic therapeutic to combat or limit infection progression caused by coronaviruses that utilize ACE2 as a receptor. If given in its soluble form as an appropriate recombinant ACE2 protein, a new tool may be at hand to combat the spread of coronavirus in susceptible individuals by limiting coronavirus attachment to the cell membranes, cell entry, and replication	753315	
3.4.17.23	medicine	angiotensin-converting enzyme 2 is a target for gene therapy for hypertension disorders	668528	
3.4.17.23	medicine	antibodies and small molecular inhibitors that can block the interaction of the enzyme (ACE2) with the receptor binding domain can to combat the virus SARS-CoV-2	752692	
3.4.17.23	medicine	binding of SARS-CoV-2 spike protein, variant omicron B.1.1.529, to ACE2 is inhibited by caffeic acid hexoside (-6.4 kcal/mol, RMSD 2.382 A) and phloretin (-6.3 kcal/mol, RMSD 0.061 A) from Sargassum wightii, which interact with crucial residues Asn417, Ser496, Tyr501, and His505 of the spike protein. 5alpha-Cholestan-3beta-ol, 2-methylene- (-6.0 kcal/mol, RMSD 3.074 A) from Corallina officinalis shows inhibitory effect against the omicron receptor-binding domain mutated residues Leu452 and Ala484	765306	
3.4.17.23	medicine	chronic treatment with the AT1R antagonist almesartan induces a fivefold increase in ACE2 mRNA in the aorta which leads to a significant increase in aortic angiotensin(1-7) protein expression. These effects are associated with significant decreases in aortic medial thickness and may represent an important protective mechanism in the prevention of cardiovascular events in hypertensive subjects	667145	
3.4.17.23	medicine	circulating extracellular vesicles that express ACE2 isolated from human plasma or cells neutralize SARS-CoV-2 infection by competing with cellular ACE2. Compared to vesicle-free recombinant human ACE2, ACE2 from extracellular vesicles shows a 135fold higher potency in blocking the binding of the viral spike protein receptor-binding domain, and a 60- to 80fold higher efficacy in preventing infections by both pseudotyped and authentic SARS-CoV-2. ACE2 from extracellular vesicles protects human ACE2 transgenic mice from SARS-CoV-2-induced lung injury and mortality. ACE2 from extracellular vesicles inhibits the infection of SARS-CoV-2 variants alpha, beta, and delta with equal or higher potency than for the wild-type strain	765453	
3.4.17.23	medicine	coexpression of intermediate filament protein vimentin with ACE2 increases SARS-CoV-2 entry in HEK-293 cells, and shRNA-mediated knockdown of vimentin significantly reduces SARS-CoV-2 infection of human endothelial cells. Incubation of A-549 cells expressing ACE2 with purified vimentin increases pseudotyped SARS-CoV-2 spike protein entry. The S-protein receptor-binding domain is sufficient for spike protein interaction with vimentin. Extracellular vimentin binds to SARS-CoV-2 spike protein and facilitates SARS-CoV-2 infection	765690	
3.4.17.23	medicine	compounds benzyl (6aS,9aS)-10-benzyl-4-[benzyl(methyl)amino]-8-(cyclopropanecarbonyl)-6a,7,8,9,9a,10-hexahydrocyclopenta[b]pyrimido[4,5-e][1,4]diazepine-6(5H)-carboxylate, benzyl (6aS,9aS)-4-[benzyl(methyl)amino]-8-(cyclopropanecarbonyl)-10-[(4-methylphenyl)methyl]-6a,7,8,9,9a,10-hexahydrocyclopenta[b]pyrimido[4,5-e][1,4]diazepine-6(5H)-carboxylate and benzyl (6aS,9aS)-4-[benzyl(methyl)amino]-10-[(4-chlorophenyl)methyl]-8-(cyclopropanecarbonyl)-6a,7,8,9,9a,10-hexahydrocyclopenta[b]pyrimido[4,5-e][1,4]diazepine-6(5H)-carboxylate inhibit the interactions between SARS-CoV-2 spike receptor-binding domain and ACE2 by modulating ACE2 without impairing its enzymatic activity necessary for normal physiological functions. The compounds suppress viral infection in cultured cells by inhibiting the entry of ancestral and variant SARS-CoV-2	763895	
3.4.17.23	medicine	differential regulation of ACE2 activity during the progression of atherosclerosis suggest that this novel molecule of the renin–angiotensin system may play a role in the pathogenesis of atherosclerosis	693806	
3.4.17.23	medicine	enhancing ACE2 action may serve to provide additional therapeutic benefits patients with cardiovascular and diabetic kidney disease. Increased ACE2 activity by the use of human recombinant ACE2 and/or a small molecule activator(xanthenone) of ACE2 may represent potential new therapies for lung, cardiovascular and kidney diseases by providing dual beneficial effects by antagonizing angiotensin II action while generating angiotensin-(1-7)	694351	
3.4.17.23	medicine	expression of ACE2 increases during aging in human lungs. ACE2 expression increases upon telomere shortening or dysfunction in cultured mammalian cells. This increase is controlled at the transcriptional level, and ACE2 promoter activity is DNA damage response-dependent. Both pharmacological global DNA damage response inhibition of ATM kinase activity and selective telomeric DNA damage response inhibition by the use of antisense oligonucleotides prevent ACE2 upregulation following telomere damage	764575	
3.4.17.23	medicine	expression of ACE2 increases during aging in lungs. ACE2 expression increases upon telomere shortening or dysfunction in mice. This increase is controlled at the transcriptional level, and ACE2 promoter activity is DNA damage response-dependent. Both pharmacological global DNA damage response inhibition of ATM kinase activity and selective telomeric DNA damage response inhibition by the use of antisense oligonucleotides prevent ACE2 upregulation following telomere damage	764575	
3.4.17.23	medicine	expression of both ACE2 and TMPRSS2 genes is necessary to support SARS-CoV-2 infection and replication in DF1 cells and a nonpermissive sub-lineage of MDCK cells. Titers of SARS-CoV-2 in these cell lines are comparable to those observed in control Vero cells. Permissive replication of SARS-CoV-2 is not found in pig or horse. Cells expressing genes from either bat species tested demonstrate temporal replication of SARS-CoV-2 that peaks early and is not sustained	765871	
3.4.17.23	medicine	identification of ACE2 as a receptor for SARS-CoV will contribute to the development of antivirals and vaccines	668221	
3.4.17.23	medicine	in lung tissues collected from mice that were sub-chronically exposed to air or 0.8 ppm ozone for three weeks, the ACE2 transcripts are significantly elevated in the parenchyma, but not in the extrapulmonary airways and alveolar macrophages. A significant proportion of additional known SARS-CoV-2 host susceptibility genes are upregulated in alveolar macrophages and parenchyma from ozone-exposed mice	765794	
3.4.17.23	medicine	inhibition of SARS-CoV-2 spike protein binding to ACE2 by a higher-affinity variant of the B38 monoclonal antibody, containing mutantion F27Q in the heavy chain (F27Q), which can bind to the rececptor-binding domain more tightly, and by Ty1 alpaca nanobody, i.e.a 38 amino acid peptide inhibitor taking components from Ty1. The peptide exhibits improved affinity for the rececptor-binding by up to 100fold, and like B38 mutant, it can outclass the binding affinity of ACE2 with the rececptor-binding domain	765099	
3.4.17.23	medicine	interaction of ACE2 and SARS-CoV-2 Omicron spike protein. The mutations in the Omicron variant at residues 493, 496, 498, and 501 restore ACE2 binding efficiency that would be lost as a result of other mutations such as K417N	765834	
3.4.17.23	medicine	interaction with Sars-CoV2 spike protein mutants. The N501Y receptor-binding domainmutant binds to ACE2 with higher affinity due to improved pi-pi stacking and pi-cation interactions. The higher binding affinity of the E484K mutant is caused by the formation of additional hydrogen bond and salt-bridge interactions with ACE2. Both the mutants bind to the B38 neutralizing antibody with reduced affinity due to the loss of several hydrogen-bonding interactions	764853	
3.4.17.23	medicine	investigation of reverse genetic-rescued SARS-CoV-2 viruses in K18-hACE2 mice. The genetic-rescued SARS-CoV-2 viruses will facilitate basic understanding of SARS-CoV-2 and the preclinical development of COVID-19 therapeutics	763415	
3.4.17.23	medicine	patients younger than 70 years old, patients with eosinophilic asthma, and inhaled corticosteroids non-users are associated with higher levels of blood serum ACE2. Blood eosinophils and fractionated exhaled nitric oxide levels are positively correlated with serum ACE2	765211	
3.4.17.23	medicine	plasma ACE2 activity independently increases the hazard of adverse long-term cardiovascular outcomes in patients with obstructive coronary artery disease. Above-median plasma ACE2 activity is associated with major adverse cardiovascular events and heart failure hospitalisation	755175	
3.4.17.23	medicine	plasma kininase II or ACE levels are significantly increased by 18% in untreated diabetics when compared with healthy volunteers. After treatment for 6 weeks with metformin hydrochloride 500 mg twice daily there is a significant decrease of 20% in their ACE levels. Plasma prekallikrein levels are raised significantly by 28% in diabetic patients in contrast with the control subjects and the levels are reduced by 44% after treatment with metformin hydrochloride. NO levels are significantly decreased in plasma by 56% and in urine by 62% in untreated diabetic patients as compared with the healthy subjects. In treated diabetic patients' samples, there is an increase of 50% in plasma and 37% in urine samples compared to untreated patients	753896	
3.4.17.23	medicine	potential important target in cardio-renal disease	657967	
3.4.17.23	medicine	potential therapeutic approach to ACE2-mediated COVID-19. Treatment with a soluble form of ACE2 may exert dual functions, slow viral entry into cells and hence viral spread and protect the lung from injury	753944	
3.4.17.23	medicine	recombinant ACE2 can protect mice from severe acute lung injury	670375	
3.4.17.23	medicine	reduction of ACE2 expression by RNA interference promotes the proliferation of cultured pancreatic cancer cells. ACE2 may have clinical potential as a novel molecular target for the treatment of pancreatic ductal adenocarcinoma	695187	
3.4.17.23	medicine	regulation of NF-kappaB and ACE2 by specific Ang II type 1 receptor AT1 and Ang II type 2 receptor AT2 antagonists in a nongenetic model of type 2 diabetic nephropathy. The AT1 receptor and AT2 receptor antagonists lead to the repression and activation of the NF-kappaB signalling pathway, respectively. The blockade of AT2 receptor leads to an increase in ACE2 expression	752845	
3.4.17.23	medicine	SARS-CoV and SARS-CoV-2 spike proteins have similar charge distributions and electrostatic features when binding with ACE2. The complex structures of ACE2 and the spike proteins of SARS-CoV/SARS-CoV-2 are stable at pH values ranging from 7.5 to 9. SARS-CoV-2 forms 19 pairs of hydrogen bonds with high occupancy to ACE2, compared to 16 pairs between SARS-CoV and ACE2. SARS-CoV viruses prefer sticking to the same hydrogen bond pairs, while SARS-CoV-2 tends to have a larger range of selections on hydrogen bonds acceptors	765500	
3.4.17.23	medicine	SARS-CoV-2 spike protein binds ACE2. A dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization has a binding affinity of 16 nM for the SARS-CoV-2 spike receptor-binding domain, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 microM	764460	
3.4.17.23	medicine	SARS-CoV-2 spike protein binds to ACE2. Bromelain-derived peptide DYGAVNEVK interacts with several critical receptor-binding domain binding residues responsible for the adhesion of the receptor-binding domain to hACE2. Molecular dynamics simulations reveal stable interactions between DYGAVNEVK and receptor-binding domain variants, as well as free binding energy calculations. The bromelain-derived peptide inhibition at the binding site of the receptor-binding domain and ACE2 is competitive	765435	
3.4.17.23	medicine	SARS-CoV-2 spike protein-ACE2 binding is strongly blocked by ritonavir and naloxegol. The two ligands stabilize both the entire receptor-binding domain and the binding site key residues, ensuring efficient blocking of the key receptor-binding domain residues which are involved in receptor-binding domain-ACE2 interaction. Naloxegol and ritonavir are the most potently blocking ligands, followed by far by sofosbuvir and remdesivir	765109	
3.4.17.23	medicine	soluble ACE2 activity is a biomarker in heart failure, and in hypertension	732780	
3.4.17.23	medicine	values of 438.1 and 219 microM ibuprofen as well as 204.7 microM flurbiprofen significantly reduce viral load in Caco-2 cells, while etoricoxib and paracetamol have no consistent, significant effect on viral load	764930	
3.4.17.23	pharmacology	ACE 2 is a potential therapeutic target in the treatment of heart failure	708649	
3.4.17.23	pharmacology	ACE2 might be a target for treatment of non-small cell lung cancer	710171	
3.4.17.23	pharmacology	conserved residues at the interface of the spike protein from three strains of coronaviruses NL63, SARS-CoV, and SARS-CoV are identified, which might act as a recognition site for ACE2 receptor. The conserved interaction sites can help in effective targeting of the ACE2 binding site by therapeutics in SARS-CoV as well as SARS-CoV-2 strain	763676	
3.4.17.23	pharmacology	design and synthesis of first potent and selective enzyme inhibitors may be useful as pharmacological tools to help understanding the biological relevance and potantial role of the enzyme in human disease	658963	
3.4.17.23	pharmacology	identification of compounds that bind to either the angiotensin converting enzyme 2 (ACE2) and/or the SARS-CoV-2 spike protein receptor binding domain (SARS-CoV-2 spike protein RBD). All 22 identified compounds provide scaffolds for the development of new chemical entities for the treatment of COVID-19	763416	
3.4.17.23	pharmacology	the binding of eighteen candidate drugs with ACE2 enzyme and [SARSCoV-2/ACE2] complex is examined by using docking analysis. The docking ranking shows that some of these ligands might have the ability to inhibit SARS-CoV-2. The study shows that Ramipril, Delapril and Lisinopril could bind with ACE2 receptor and [SARSCoV-2/ACE2] complex better than chloroquine and hydroxychloroquine	763280