Abstract
Studies have shown that injection of recombinant angiotensin-converting enzyme 2 (ACE2) significantly increased circulatory levels of ACE2 activity, reduced cardiac hypertrophy and fibrosis, and effectively lowered blood pressure. In addition, recombinant ACE2 ameliorated albuminuria and might contribute to renal protection. Meanwhile, potential pharmacological treatments based on ACE2 are attracting increasing attention from scientists following a growing understanding of the role of the ACE2 receptor in the pathogenesis of coronavirus disease 2019 (COVID-19). In this article, we comprehensively summarized the literature on the structure, distribution, and function of ACE2. More importantly, we draw a conclusion that ACE2 decoys such as sACE2, hrsACE2 and ACE2-derived peptides, drugs down-regulating the ACE2 or TMPRSS2 gene expression, and the application of epigenetic modifiers and Traditional Chinese Medicine might represent promising approaches for the future of COVID-19 treatment.
Keywords: ACE2 therapy, SARS-CoV-2, COVID-19, rACE2, ACE2-derived peptides, TMPRSS2.
[http://dx.doi.org/10.1101/2020.04.07.024752]
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[http://dx.doi.org/10.1126/science.abb2762] [PMID: 32132184]
[http://dx.doi.org/10.1007/s00401-019-02098-6] [PMID: 31982938]
[http://dx.doi.org/10.1164/rccm.201712-2570OC] [PMID: 29570986]
[http://dx.doi.org/10.7150/ijms.48096] [PMID: 33029102]
[http://dx.doi.org/10.1038/s41467-020-14867-z] [PMID: 32103002]
[http://dx.doi.org/10.1161/01.RES.87.5.e1] [PMID: 10969042]
[http://dx.doi.org/10.1007/s11064-018-2679-4] [PMID: 30443713]
[http://dx.doi.org/10.1074/jbc.M002615200] [PMID: 10924499]
[http://dx.doi.org/10.1515/cclm-2020-0727] [PMID: 32598305]
[http://dx.doi.org/10.1016/j.meegid.2021.104773] [PMID: 33607284]
[http://dx.doi.org/10.1074/jbc.M311191200] [PMID: 14754895]
[http://dx.doi.org/10.3390/ijms18030563] [PMID: 28273875]
[http://dx.doi.org/10.1016/j.cgh.2020.04.040] [PMID: 32334082]
[http://dx.doi.org/10.1007/s11739-020-02364-6] [PMID: 32430651]
[http://dx.doi.org/10.1038/s41591-020-0868-6] [PMID: 32327758]
[http://dx.doi.org/10.1152/ajpregu.00292.2006] [PMID: 16946085]
[http://dx.doi.org/10.15252/msb.20209610] [PMID: 32715618]
[http://dx.doi.org/10.1093/molehr/gaaa030] [PMID: 32365180]
[http://dx.doi.org/10.1016/j.celrep.2020.108175] [PMID: 32946807]
[http://dx.doi.org/10.1002/path.1570] [PMID: 15141377]
[http://dx.doi.org/10.2174/156800911795538110] [PMID: 21395550]
[http://dx.doi.org/10.1016/j.tifs.2017.07.011]
[http://dx.doi.org/10.2174/1871528113666140713164506] [PMID: 25019157]
[http://dx.doi.org/10.1016/j.tips.2004.04.001] [PMID: 15165741]
[http://dx.doi.org/10.1210/en.2003-0150] [PMID: 12746271]
[http://dx.doi.org/10.1186/s43042-020-00099-9]
[http://dx.doi.org/10.1042/cs1000481]
[http://dx.doi.org/10.1038/sj.jhh.1001436] [PMID: 12140725]
[http://dx.doi.org/10.1080/08037050310001057] [PMID: 12797627]
[http://dx.doi.org/10.1097/MNH.0b013e328341164a] [PMID: 21099686]
[PMID: 27469342]
[http://dx.doi.org/10.1016/j.cardiores.2006.09.006] [PMID: 17049503]
[http://dx.doi.org/10.1016/j.biopha.2021.111363]
[http://dx.doi.org/10.15252/msb.202110232]
[http://dx.doi.org/10.1016/j.pharmthera.2010.06.003] [PMID: 20599443]
[http://dx.doi.org/10.1074/jbc.M006723200] [PMID: 11278314]
[http://dx.doi.org/10.1038/nature05475] [PMID: 17167413]
[http://dx.doi.org/10.1053/j.gastro.2008.10.055] [PMID: 19185582]
[http://dx.doi.org/10.3343/alm.2021.41.2.129] [PMID: 33063674]
[http://dx.doi.org/10.1371/journal.pone.0184845] [PMID: 28915252]
[http://dx.doi.org/10.1038/nature11228] [PMID: 22837003]
[http://dx.doi.org/10.1002/path.5471] [PMID: 32418199]
[http://dx.doi.org/10.1016/j.cell.2020.09.018] [PMID: 32979942]
[http://dx.doi.org/10.1074/jbc.RA120.015303] [PMID: 33122196]
[http://dx.doi.org/10.1038/s41423-020-0400-4] [PMID: 32203189]
[http://dx.doi.org/10.1007/s00018-020-03580-1] [PMID: 32623480]
[http://dx.doi.org/10.1038/s41392-020-00369-3] [PMID: 33127889]
[http://dx.doi.org/10.1126/science.abd5223] [PMID: 32817270]
[http://dx.doi.org/10.1016/j.molcel.2020.04.022] [PMID: 32362314]
[http://dx.doi.org/10.1007/s11427-020-1637-5] [PMID: 32009228]
[http://dx.doi.org/10.1038/s41586-020-2179-y] [PMID: 32225175]
[http://dx.doi.org/10.1038/s41580-021-00418-x] [PMID: 34611326]
[http://dx.doi.org/10.1016/j.jbc.2021.100306] [PMID: 33476648]
[http://dx.doi.org/10.1038/s41392-021-00653-w] [PMID: 34117216]
[http://dx.doi.org/10.3390/v15020525] [PMID: 36851739]
[http://dx.doi.org/10.1038/nm1267] [PMID: 16007097]
[http://dx.doi.org/10.1038/nature03712] [PMID: 16001071]
[http://dx.doi.org/10.1016/j.kint.2020.04.009] [PMID: 32354636]
[http://dx.doi.org/10.3390/jcm11226799] [PMID: 36431276]
[http://dx.doi.org/10.1016/j.omtm.2022.07.003] [PMID: 35818571]
[http://dx.doi.org/10.15252/emmm.202216109] [PMID: 36094679]
[http://dx.doi.org/10.1002/advs.202201294] [PMID: 35896894]
[http://dx.doi.org/10.1038/s41392-020-00374-6] [PMID: 33144565]
[http://dx.doi.org/10.1016/j.cell.2020.04.004] [PMID: 32333836]
[http://dx.doi.org/10.1016/S2213-2600(20)30418-5] [PMID: 33131609]
[http://dx.doi.org/10.1016/j.antiviral.2022.105383] [PMID: 35917969]
[http://dx.doi.org/10.1515/hsz-2021-0426] [PMID: 35357791]
[http://dx.doi.org/10.1002/cbic.202200372] [PMID: 35785462]
[http://dx.doi.org/10.1016/j.ejmech.2023.115118] [PMID: 36682293]
[PMID: 36470304]
[http://dx.doi.org/10.1016/j.bcp.2021.114564] [PMID: 33872570]
[http://dx.doi.org/10.3390/nu13072321] [PMID: 34371831]
[http://dx.doi.org/10.1038/s41423-021-00698-5] [PMID: 34059790]
[http://dx.doi.org/10.1016/j.jve.2022.100307] [PMID: 36514715]
[http://dx.doi.org/10.1080/15592294.2020.1796896] [PMID: 32686577]
[http://dx.doi.org/10.3389/fcimb.2020.00290] [PMID: 32574283]
[http://dx.doi.org/10.1007/s43440-022-00432-6] [PMID: 36401119]
[http://dx.doi.org/10.1097/00005176-200108000-00014] [PMID: 11568519]
[http://dx.doi.org/10.1016/j.intimp.2010.06.012] [PMID: 20601181]
[http://dx.doi.org/10.3390/nu14020274] [PMID: 35057455]
[http://dx.doi.org/10.1080/10408398.2014.905450] [PMID: 25629818]
[http://dx.doi.org/10.1080/07391102.2022.2158934] [PMID: 36591650]
[http://dx.doi.org/10.1007/s12602-021-09879-0] [PMID: 34837166]
[http://dx.doi.org/10.1007/s00228-020-02963-4] [PMID: 32696234]
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[http://dx.doi.org/10.1128/AAC.00754-20] [PMID: 32312781]
[http://dx.doi.org/10.1002/jmv.28124] [PMID: 36056630]
[http://dx.doi.org/10.3390/ijms232012522] [PMID: 36293378]
[PMID: 10485450]
[http://dx.doi.org/10.3389/fcvm.2022.957340] [PMID: 36187008]