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Infectious Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Review Article

Recombinant ACE2 - Opportunities and Challenges in COVID-19 Treatment

In Press, (this is not the final "Version of Record"). Available online 18 April, 2024
Author(s): Mandeep Kaur*, Rahul Sandhu and Akriti Aggarwal
Published on: 18 April, 2024

Article ID: e180424229061

DOI: 10.2174/0118715265298816240321045741

Price: $95

Abstract

It was in 2019 that the world experienced the devastation caused by SARS-COV-2, contributing to a large number of deaths. This contagious virus not only challenged the health care system but has also hit the economy very badly. There has been a lot of research on effective vaccine development, and there has been some success in the same, but no effective antiviral drugs are available in the market. No doubt vaccination can prevent the disease, but it doesn’t have the potential to cure an infected person, for which there is a dire need to develop some effective drug. Angiotensin convertase enzyme 2 (ACE2) played a substantial role in SARS-COV2 pathogenesis and thus has gained much attention during the pandemic. Moreover, it has opened up new avenues for the cure of COVID-19.

[1]
Abduljalil JM, Abduljalil BM. Epidemiology, genome, and clinical features of the pandemic SARS-CoV-2: A recent view. New Microbes New Infect 2020; 35: 100672.
[http://dx.doi.org/10.1016/j.nmni.2020.100672] [PMID: 32322400]
[2]
COVID-19 epidemological update 27 october 2023 WHO. 2023. Available from: https:/www.who.int/publications/m/item/covid(Accessed 25 November 2023).
[3]
Cheng H, Wang Y, Wang GQ. Organ‐protective effect of angiotensin‐converting enzyme 2 and its effect on the prognosis of COVID‐19. J Med Virol 2020; 92(7): 726-30.
[http://dx.doi.org/10.1002/jmv.25785] [PMID: 32221983]
[4]
Tolouian R, Zununi Vahed S, Ghiyasvand S, Tolouian A, Ardalan M. COVID-19 interactions with angiotensin-converting enzyme 2 (ACE2) and the kinin system; looking at a potential treatment. J Renal Inj Prev 2020; 9(2): e19.
[http://dx.doi.org/10.34172/jrip.2020.19]
[5]
Gurwitz D. Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics. Drug Dev Res 2020; 81(5): 537-40.
[http://dx.doi.org/10.1002/ddr.21656] [PMID: 32129518]
[6]
Passos-Silva DG, Verano-Braga T, Santos RAS. Angiotensin-(1–7): Beyond the cardio-renal actions. Clin Sci 2013; 124(7): 443-56.
[http://dx.doi.org/10.1042/CS20120461] [PMID: 23249272]
[7]
Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci 2020; 248: 117477.
[http://dx.doi.org/10.1016/j.lfs.2020.117477] [PMID: 32119961]
[8]
Wang K, Gheblawi M, Oudit GY. Angiotensin converting enzyme 2: A double-edged sword. Circulation 2020; 142(5): 426-8.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047049] [PMID: 32213097]
[9]
Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395(10224): 565-74.
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[10]
Haschke M, Schuster M, Poglitsch M, et al. Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects. Clin Pharmacokinet 2013; 52(9): 783-92.
[http://dx.doi.org/10.1007/s40262-013-0072-7] [PMID: 23681967]
[11]
Yang M. Cell pyroptosis, a potential pathogenic mechanism of 2019-nCoV infection. In: Department of Ophthalmology. The University of Hong Kong 2020; pp. 1-7.
[http://dx.doi.org/10.2139/ssrn.3527420]
[12]
Fu Y, Cheng Y, Wu Y. Understanding SARS-CoV-2 mediated inflammatory responses: from mechanisms to potential therapeutic tools. Virol Sin 2020; 35(3): 266-71.
[http://dx.doi.org/10.1007/s12250-020-00207-4] [PMID: 32125642]
[13]
Jia HP, Look DC, Tan P, et al. Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia. Am J Physiol Lung Cell Mol Physiol 2009; 297(1): L84-96.
[http://dx.doi.org/10.1152/ajplung.00071.2009] [PMID: 19411314]
[14]
Bombardini T, Picano E. Angiotensin-converting enzyme 2 as the molecular bridge between epidemiologic and clinical features of COVID-19. Can J Cardiol 2020; 20: 30299-300.
[15]
Tikellis C, Thomas MC. Angiotensin-converting enzyme 2 (ACE2) is a key modulator of the renin angiotensin system in health and disease. Int J Pept 2012; 2012: 1-8.
[http://dx.doi.org/10.1155/2012/256294] [PMID: 22536270]
[16]
Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020; 5(4): 562-9.
[http://dx.doi.org/10.1038/s41564-020-0688-y] [PMID: 32094589]
[17]
Arendse LB, Danser AHJ, Poglitsch M, et al. Novel therapeutic approaches targeting the renin-angiotensin system and associated peptides in hypertension and heart failure. Pharmacol Rev 2019; 71(4): 539-70.
[http://dx.doi.org/10.1124/pr.118.017129] [PMID: 31537750]
[18]
Guignabert C, de Man F, Lombès M. ACE2 as therapy for pulmonary arterial hypertension: The good outweighs the bad. Eur Respir J 2018; 51(6): 1800848.
[http://dx.doi.org/10.1183/13993003.00848-2018] [PMID: 29929959]
[19]
Kazemi-Bajestani SMR, Patel VB, Wang W, Oudit GY. Targeting the ACE2 and apelin pathways are novel therapies for heart failure: Opportunities and challenges. Cardiol Res Pract 2012; 2012: 1-11.
[http://dx.doi.org/10.1155/2012/823193] [PMID: 22655211]
[20]
Batlle D, Wysocki J, Satchell K. Soluble angiotensin-converting enzyme 2: A potential approach for coronavirus infection therapy? Clin Sci 2020; 134(5): 543-5.
[http://dx.doi.org/10.1042/CS20200163] [PMID: 32167153]
[21]
Şı̇mşek Yavuz S, Komşuoğlu Çelı̇kyurt İ. An update of anti-viral treatment of COVID-19. Turk J Med Sci 2021; 51(SI-1): 3372-90.
[http://dx.doi.org/10.3906/sag-2106-250] [PMID: 34391321]
[22]
Zhang H, Lv P, Jiang J, et al. Advances in developing ACE2 derivatives against SARS-CoV-2. Lancet Microbe 2023; 4(5): e369-78.
[http://dx.doi.org/10.1016/S2666-5247(23)00011-3] [PMID: 36934742]
[23]
Yamaguchi T, Hoshizaki M, Minato T, et al. ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury. Nat Commun 2021; 12(1): 6791.
[http://dx.doi.org/10.1038/s41467-021-27097-8] [PMID: 34815389]
[24]
Zoufaly A, Poglitsch M, Aberle JH, et al. Human recombinant soluble ACE2 in severe COVID-19. Lancet Respir Med 2020; 8(11): 1154-8.
[http://dx.doi.org/10.1016/S2213-2600(20)30418-5] [PMID: 33131609]
[25]
Shoemaker RH, Panettieri RA Jr, Libutti SK, et al. Development of an aerosol intervention for COVID-19 disease: Tolerability of soluble ACE2 (APN01) administered via nebulizer. PLoS One 2022; 17(7): e0271066.
[http://dx.doi.org/10.1371/journal.pone.0271066] [PMID: 35816490]
[26]
Daniell H, Nair SK, Esmaeili N, et al. Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection. Mol Ther 2022; 30(5): 1966-78.
[http://dx.doi.org/10.1016/j.ymthe.2021.11.008] [PMID: 34774754]
[27]
Linsky TW, Vergara R, Codina N, et al. De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2. Science 2020; 370(6521): 1208-14.
[http://dx.doi.org/10.1126/science.abe0075] [PMID: 33154107]
[28]
Kruse RL. Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China. F1000 Res 2020; 9: 72.
[http://dx.doi.org/10.12688/f1000research.22211.2] [PMID: 32117569]
[29]
Aboul-Fotouh S, Mahmoud AN, Elnahas EM, Habib MZ, Abdelraouf SM. What are the current anti-COVID-19 drugs? From traditional to smart molecular mechanisms. Virol J 2023; 20(1): 241.
[http://dx.doi.org/10.1186/s12985-023-02210-z] [PMID: 37875904]
[30]
Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19). JAMA 2020; 323(18): 1824-36.
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID: 32282022]
[31]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[32]
NIH. Coronavirus disease 2019 (COVID‑19) treatment guidelines. 2019. Available from : https:// www. covid 19treatmentguidelines. nih. gov/ (Accessed 3 Oct 2023).
[33]
IDSA,. IDSA guidelines on the treatment and management of patients with COVID-19 2023. Available from: https:// www. idsociety.org/ (Accessed 3 Oct 2023).
[34]
NICE. COVID‑19 rapid guideline: managing COVID‑19. NICE guideline. 2021. Available from: https:// www. nice. org (Accessed 3 Oct 2023).
[35]
FDA approves first oral antiviral for treatment of COVID-19 in adults Available from: https:// www. fda. gov/ (Accessed 3 Oct 2023).
[36]
Zarenezhad E, Marzi M. Review on molnupiravir as a promising oral drug for the treatment of COVID-19. Med Chem Res 2022; 31(2): 232-43.
[http://dx.doi.org/10.1007/s00044-021-02841-3] [PMID: 35002192]
[37]
Baum A, Ajithdoss D, Copin R, et al. REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters. Science 2020; 370(6520): 1110-5.
[http://dx.doi.org/10.1126/science.abe2402] [PMID: 33037066]
[38]
Jones BE, Brown-Augsburger PL, Corbett KS, Westendorf K, Davies J, Cujec TP. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med 2021; 13(593): 1-1906.
[39]
FDA. EVUSHELD (tixagevimab co‑packaged with cilgavimab) EAU fact sheet for health care providers. Available from: https:// www. fda. gov/ media/ 154701/ (Accessed 3 Oct 2023).
[40]
FDA. bamlanivimab/etesevimab EAU fact sheet for health care providers. Available from: https:// www. fda. gov/ media/ 145802/ (Accessed 3 Oct 2023).
[41]
FDA. casirivimab/ imdevimab EAU fact sheet for health care providers. Available from: https:// www. fda. gov/ media/ 145611/ (Accessed 3 Oct 2023).
[42]
FDA. Sotrovimab EAU fact sheet for health care providers. Available from: https:// www. fda. gov/ media/ 149534/ (Accessed 3 Oct 2023).
[43]
FDA. Bebtelovimab EAU fact sheet for health care providers. Available from: https:// www. fda. gov/ media/ 156152/ (Accessed 3 Oct 2023).
[44]
FDA. Coronavirus (COVID‑19) Update: FDA revokes emergency use authorization for monoclonal antibody bamlanivimab. Available from: https:// www. fda. gov/ (Accessed 3 Oct 2023).
[45]
FDA. Coronavirus (COVID‑19) Update: FDA limits use of certain monoclonal antibodies to treat COVID‑19 due to the omicron variant. Available from: https:// www. fda. gov/ (Accessed 3 Oct 2023).
[46]
FDA. FDA updates Sotrovimab emergency use authorization Available from: https:// www. fda. gov/ drugs/ (Accessed 3 Oct 2023).
[47]
FDA. FDA announces bebtelovimab is not currently authorized in any US region. Available from: https:// www. fda. gov/ drugs/ (Accessed 3 Oct 2023).
[48]
FDA announces Evusheld is not currently authorized for emergency use in the U.S. Available from: https:// www. fda. gov/ drugs/ (Accessed 3 Oct 2023).
[49]
van Griensven J, Edwards T, de Lamballerie X, et al. Evaluation of convalescent plasma for ebola virus disease in guinea. N Engl J Med 2016; 374(1): 33-42.
[http://dx.doi.org/10.1056/NEJMoa1511812] [PMID: 26735992]
[50]
Yoshikawa T, Hill T, Li K, Peters CJ, Tseng CTK. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol 2009; 83(7): 3039-48.
[http://dx.doi.org/10.1128/JVI.01792-08] [PMID: 19004938]
[51]
FDA roundup. 2022. Available from: https:// www. fda. gov/ (Accessed 3 Oct 2023).
[52]
Generali D, Bosio G, Malberti F, et al. Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study. Int J Infect Dis 2021; 104: 433-40.
[http://dx.doi.org/10.1016/j.ijid.2020.12.073] [PMID: 33385581]
[53]
FDA. Anakinra EUA fact sheet for health care providers Available from: https:// www. fda. gov/ media/ 163075/ (Accessed 3 Oct 2023).
[54]
FDA. Authorizes Gohibic (vilobelimab) injection for the treatment of COVID‑19. Available from: https:// www. fda. gov/ drugs/ (Accessed 3 Oct 2023).
[55]
Labandeira-Garcia JL, Labandeira CM, Valenzuela R, Pedrosa MA, Quijano A, Rodriguez-Perez AI. Drugs modulating renin-angiotensin system in COVID-19 treatment. Biomedicines 2022; 10(2): 502.
[http://dx.doi.org/10.3390/biomedicines10020502] [PMID: 35203711]
[56]
Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020; 181(4): 905-913.e7.
[http://dx.doi.org/10.1016/j.cell.2020.04.004] [PMID: 32333836]
[57]
Hussain M, Jabeen N, Raza F, et al. Structural variations in human ACE2 may influence its binding with SARS‐CoV‐2 spike protein. J Med Virol 2020; 92(9): 1580-6.
[http://dx.doi.org/10.1002/jmv.25832] [PMID: 32249956]
[58]
Cao Y, Li L, Feng Z, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov 2020; 6(1): 11.
[http://dx.doi.org/10.1038/s41421-020-0147-1] [PMID: 32133153]

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