In December 2019, a novel infectious disease, caused by Severe Acute Respiratory Syndrome-coronavirus 2 (SARS-CoV-2), was identified in Wuhan, China, now declared as a pandemic. The Renin–Angiotensin system (RAS) and angiotensin-converting enzyme 2 (ACE2) have drawn special attention, as ACE2 acts as a receptor for SARS-CoV2. No specific therapy against SARS-COV2 has been invented yet. There is a constant need towards understanding of the underlying pathophysiology to aid the pharmacological research. We have looked at the current evidence on the relationship between SARS-COV-2 and RAS and ACE2. Articles in English language published between 1st January 2003 and 15th June 2020 were searched using keywords and MeSH (Medical Subject Heading). We used Google Scholar and Pubmed as search engines. Conclusion: Bats serve as primary reservoir for SARS-CoV2, but its intermediate host has not been identified yet. ‘Hot spots’ on ACE2, serve as receptors for SARS-COV2. Imbalance in the activity of ACE/ACE2 is an important contribution towards the pathogenesis of coronavirus related diseases. ACE2 also has protective role and recombinant ACE2 has been shown to improve lung injury and it is a potential therapeutic agent.
| Published in | American Journal of Internal Medicine (Volume 8, Issue 4) |
| DOI | 10.11648/j.ajim.20200804.14 |
| Page(s) | 159-171 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2020. Published by Science Publishing Group |
Renin-Angiotensin System, Angiotensin Converting Enzyme-2, Lung Inflammation, SARS-COV, Angiotensin-II
| [1] | Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020; 382 (8), 727−733. |
| [2] | Srinivasan S, Cui H, Gao Z, et al. Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins. Viruses 2020, 12, 360. |
| [3] | Galante O, Avni YS, Fuchs L, Ferster OA, Almog Y. Coronavirus NL63-induced Adult Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2016 Jan 1; 193 (1): 100-1. https://doi.org/10.1164/rccm.201506-1239LE. |
| [4] | Wang H, Li X, Li T, et al. The genetic sequence, origin, and diagnosis of SARS-CoV-2. Eur J Clin Microbiol Infect Dis 2020; 1-7. doi: 10.1007/s10096-020-03899-4. |
| [5] | Huang C, Wang Y, Li X, Ren L, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China: 2020. Lancet. 2020 Feb 15; 395 (10223): 497-506. https://doi.org/10.1016/S0140-6736(20)30183-5. |
| [6] | Zhou P, Yang XL, Wang XG, at al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7. |
| [7] | Banerjee A, Kulcsar K, Misra V, Frieman M, Mossman K. Bats and Coronaviruses. Viruses. 2019; 11 (1): 41. Published 2019 Jan 9. doi: 10.3390/v11010041. |
| [8] | Haagmans BL, Al Dhahiry SH, Reusken CB, et al. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect. Dis. 2014; 14: 140–145. |
| [9] | Hou Y, Peng C, Yu M, et al. Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry. Arch Virol 2020; 155, 1563–1569. https://doi.org/10.1007/s00705-010-0729-6. |
| [10] | Zhang T, Wu Q, Zhang Z, Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak, Current Biology, Volume 30, Issue 7, 2020, Pages 1346-1351.e2, https://doi.org/10.1016/j.cub.2020.03.022. |
| [11] | Yang XL, Hu B, Wang B, et al. Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus. J. Virol. 2015; 90: 3253–3256. |
| [12] | Kan B, Wang M, Jing H, et al. Molecular evolution analysis and geographic investigation of severe acute respiratory syndrome coronavirus-like virus in palm civets at an animal market and on farms. J. Virol. 2005; 79: 11892–11900. |
| [13] | Lam, T. T., Shum, M. H., Zhu, H. et al. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature (2020). https://doi.org/10.1038/s41586-020-2169-0. |
| [14] | Liu, Z, Xiao, X, Wei, X, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol. 2020; 92: 595–601. https://doi.org/10.1002/jmv.25726. |
| [15] | Xuhua X, Extreme Genomic CpG Deficiency in SARS-CoV-2 and Evasion of Host Antiviral Defense, Molecular Biology and Evolution, msaa 094. https://doi.org/10.1093/molbev/msaa094. |
| [16] | Shil J, Wen Z, Zhong G, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2. Science 08 Apr 2020; eabb 7015. DOI: 10.1126/science.abb7015. |
| [17] | Hu B, Zeng LP, Yang XL, Ge XY, et al. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PloS Pathog. 2017; 13: e1006698. |
| [18] | Kirchdoerfer RN, Cottrell CA, Wang N, et al. Pre-fusion structure of a human coronavirus spike protein. Nature. 2016; 531: 118–121. |
| [19] | Millet JK., Whittaker GR. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Proc. Natl. Acad. Sci. USA. 2014; 111: 15214–15219. |
| [20] | Walls AC, Tortorici MA, Snijder J, et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl. Acad. Sci. USA. 2017; 114: 11157–11162. |
| [21] | Bertram S, Glowacka I, Müller MA, et al. Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease. J Virol. 2011; 85 (24): 13363-13372. Doi:10.1128/JVI.05300-11. |
| [22] | Matsuyama S, Nagata N, Shirato K, Kawase M, Takeda M, Taguchi F. Efficient Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by the Transmembrane Protease TMPRSS2. Journal of Virology Nov 2010; 84 (24) 12658-12664; https://doi.org/10.1128/JVI.01542-10. |
| [23] | Walls AC, Tortorici MA, Frenz B, et al. Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy. Nat. Struct. Mol. Biol. 2016; 23: 899–905. |
| [24] | Xiong X., Tortorici M. A., Snijder J., Yoshioka C., Walls A. C., Li W., McGuire A. T., Rey F. A., Bosch B. J., Veesler D. Glycan shield and fusion activation of a eltacoronavirus spike glycoprotein fine-tuned for enteric infections. J. Virol. 2018; 92: e01628-17. |
| [25] | Walls AC, Xiong X, Park YJ, et al. Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. Cell. 2019; 176: 1026–1039. |
| [26] | Ou X, Liu Y, Lei X, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 2020; 11, 1620. https://doi.org/10.1038/s41467-020-15562-9. |
| [27] | Wu K, Chen L, Peng G, et al. A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses. Journal of Virology May 2011, 85 (11) 5331-5337; DOI: 10.1128/JVI.02274-10 |
| [28] | Danilczyk U, Penninger JM. Angiotensin-converting enzyme II in the heart and the kidney. Circ Res 2006; 98: 463–471. |
| [29] | Gwathmey TM, Westwood BM, Pirro NT, et al. Nuclear angiotensin-(1-7) receptor is functionally coupled to the formation of nitric oxide. Am J Physiol Renal Physiol 2010; 299: F983–F990. |
| [30] | Chappell MC. Nonclassical renin-angiotensin system and renal function. Compr Physiol 2012; 2: 2733–2752. |
| [31] | Zhang H, Baker A. Recombinant human ACE2: acing out angiotensin II in ARDS therapy. Critical Care 2017; Dec 13; 21 (1): 305. doi: 10.1186/s13054-017-1882-z. |
| [32] | Gonzalez NC, Allen J, Schmidt EJ, Casillan AJ, Orth T, Wood JG: Role of the renin-angiotensin system in the systemic microvascular inflammation of alveolar hypoxia. Am J Physiol Heart Circ Physiol. 2007; 292: H2285–H2294. |
| [33] | Xie X, Chen J, Wang X, Zhang F, Liu Y: Age and gender-related difference of ACE2 expression in rat lung. Life Sci 2006; 78: 2166–2171. |
| [34] | Chen K, Bi J, Su Y, Chappell MC, Rose JC: Sex-specific changes in renal angiotensin-converting enzyme and angiotensin-converting enzyme 2 gene expression and enzyme activity at birth and over the first year of life. Reprod Sci 2016; 23 (2): 200–210. |
| [35] | Abrie JA, Moolman WJA, Cozier GE, et al. Investigation into the Mechanism of Homo- and Heterodimerization of Angiotensin-Converting Enzyme. Mol Pharmacol. 2018 Apr; 93 (4): 344-354. doi: 10.1124/mol.117.110866. |
| [36] | Schmaier AH: The kallikrein-kinin and the renin-angiotensin systems have a multi-layered interaction. Am J Physiol Regul Integr Comp Physiol 2003; 285: R1–R13. |
| [37] | Burrell LM, Johnston CI, Tikellis C, Cooper ME. ACE2, a new regulator of the renin-angiotensin system. Trends Endocrinol Metab. 2004; 15 (4): 166–169. https://doi.org/ 10.1016/j.tem.2004.03.001. |
| [38] | Vickers C, Hales P, Kaushik V, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002; Apr 26; 277 (17): 14838-43. |
| [39] | Bader M. ACE2, angiotensin- (1–7), and Mas: the other side of the coin. Pflugers Arch – Eur J Physiol 465, 79–85 (2013). https://doi.org/10.1007/s00424-012-1120-0. |
| [40] | Nehme A, Zouein FA, Zayeri ZD, Zibara K. An Update on the Tissue Renin Angiotensin System and Its Role in Physiology and Pathology. J Cardiovasc Dev Dis. 2019; 6 (2):14. https://doi.org/10.3390/jcdd6020014. |
| [41] | Wang H, Yang P, Liu K, et al. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res 2008; 18: 290–301. |
| [42] | Jia HP, Look DC, Shi L, Hickey M, et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol 2005; 79: 14614–14621. |
| [43] | Zou Z, Yan Y, Shu Y, et al. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun 2014; 5, 3594. https://doi.org/10.1038/ncomms4594. |
| [44] | Yang P, Gu H, Zhao Z, et al. Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury. Sci Rep 2015; 4, 7027. https://doi.org/10.1038/srep07027. |
| [45] | Gorovits, B., Fiscella, M., Havert, M. et al. Recommendations for the Development of Cell-Based Anti-Viral Vector Neutralizing Antibody Assays. AAPS J 22, 24 (2020). https://doi.org/10.1208/s12248-019-0403-1. |
| [46] | Liao K, Sikkema D, Wang C, Lee TN. Development of an enzymatic assay for the detection of neutralizing antibodies against therapeutic angiotensin-converting enzyme 2 (ACE2), Journal of Immunological Methods. 2012; 10.1016/j.jim..12.010, 389, 1-2, (52-60). |
| [47] | Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol 2020. doi: 10.1001/jamacardio.2020.1286. |
| [48] | Gaddam RR, Chambers S, Bhatia M. ACE and ACE2 in inflammation: a tale of two enzymes. Inflamm Allergy Drug Targets. 2014; 13:224–234. |
| [49] | Liu F, Gao F, Li Q, Liu Z. The functional study of human umbilical cord mesenchymal stem cells harbouring angiotensin-converting enzyme 2 in rat acute lung ischemia-reperfusion injury model. Cell Biochem Funct 2014; 32:580–589. |
| [50] | To KF, Lo AWI. Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS-CoV) and its putative receptor, angiotensin-converting enzyme 2 (ACE2) https://doi.org/10.1002/path.1597. |
| [51] | Asperen WV, Lutter RM, Specht R, et al. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin- (1–7) or an angiotensin II receptor antagonist. J. Pathol. 2011; 225: 618-627. Doi: 10.1002/path.2987. |
| [52] | Sodhi CP, Wohlford-Lenane C, Yamaguchi Y, et al. Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration. Am J Physiol Lung Cell Mol Physiol. 2018; 314 (1): L17-L31. Doi:10.1152/ajplung.00498.2016. |
| [53] | Li Y, Zeng Z, Li Y, et al. Angiotensin-Converting Enzyme Inhibition Attenuates Lipopolysaccharide-Induced Lung Injury by Regulating the Balance Between Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 and Inhibiting Mitogen-Activated Protein Kinase Activation. Shock. 2015 Apr; 43 (4): 395-404. doi: 10.1097/SHK.0000000000000302. |
| [54] | Kailang Wu, Lang Chen, Guiqing Peng, et al. A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses. Journal of Virology 2011; 85 (11) 5331-5337. DOI: 10.1128/JVI.02274-10. |
| [55] | Jia H. Pulmonary Angiotensin-Converting Enzyme 2 (ACE2) and Inflammatory Lung Disease, Shock: September 2016 – Volume 46 – Issue 3 – p 239-248 doi: 10.1097/SHK.0000000000000633. |
| [56] | Liu X, Yang N, Tang J, Liu S, Luo D, Duan Q, Wang X: Downregulation of angiotensin-converting enzyme 2 by the neuraminidase protein of influenza A H1N1) virus. Virus Res 185:64–71, 2014. |
| [57] | Lambert DW, Yarski M, Warner FJ, et al. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome corona virus (SARS-CoV) receptor, angiotensin-converting enzyme-2. J Biol Chem. 2005 Aug 26; 280 (34): 30113-9. |
| [58] | Jia HP, Look DC, Tan P, Shi L, Hickey M, et al. Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia. Am J Physiol Lung Cell Mol Physiol 2009; 297: L84–L96. |
| [59] | Imai, Y., Kuba, K., Rao, S. et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 436, 112–116 (2005). https://doi.org/10.1038/nature03712. |
| [60] | Treml B, Neu N, Kleinsasser A, et al. Recombinant angiotensin converting enzyme 2 improves pulmonary blood flow and oxygenation in lipopolysaccharide-induced lung injury in piglets. Crit Care Med 2010; 38: 596–601. |
| [61] | Kuhn JH, Li W, Choe H, Farzan M. Angiotensin-converting enzyme 2. A functional receptor for SARS coronavirus. Cellular and Molecular Life Sciences CMLS. 2004; 61 (21): 2738-2743. DOI: 10.1007/s00018-004-4242-5. |
| [62] | Wang D, Chai XQ, Magnussen CG, et al. Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation. Pulm Pharmacol Ther. 2019; 58: 101833. Doi: 10.1016/j.pupt.2019.101833. |
| [63] | Wiener R. S. Angiotensin converting enzyme 2 is primarily epithelial and is developmentally regulated in the mouse lung. J. Cell. Biochem. 2007; 101 (5): 1278–1291. |
| [64] | Annoni F, Orbegozo Cortés D, Irazabal M, et al. Angiotensin converting enzymes in patients with acute respiratory distress syndrome. Intensive Care Med Exp. 2015; 3 (Suppl 1): A91. doi:10.1186/2197-425X-3-S1-A91. |
| [65] | Marshall RP. Angiotensin converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 2002; 166 (5): 646–650. |
| [66] | Jerng JS. Polymorphism of the angiotensin-converting enzyme gene affects the outcome of acute respiratory distress syndrome. Crit. Care Med. 2006; 34 (4): 1001–1006. |
| [67] | Wosten-van Asperen R. M. Imbalance between pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in acute respiratory distress syndrome. Pediatr. Crit. Care Med. 2013; 14 (9): e438–e441. |
| [68] | Calfee CS, Gallagher D, Abbott J, Thompson BT, Matthay MA, Network NA. Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic significance. Critical care medicine. 2012; 40 (6): 1731. https://doi.org/10.1097/CCM.0b013e3182451c87. PMID: 22610178. |
| [69] | Levitt JE, Gould MK, Ware LB, Matthay MA. Analytic review: the pathogenetic and prognostic value of biologic markers in acute lung injury. Journal of intensive care medicine. 2009; 24 (3): 151–67. https://doi.org/10.1177/0885066609332603. PMID: 19282296. |
| [70] | Aronson JK, Ferner RE. Drugs and the renin-angiotensin system in covid-19. BMJ. 2020; 369: m1313. Doi: 10.1136/bmj.m1313. |
| [71] | Wosten-van Asperen RM, Lutter R, Specht PA, Moll GN, van Woensel JB, van der Loos CM, et al. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin- (1–7) or an angiotensin II receptor antagonist. The Journal of pathology. 2011; 225 (4): 618-27. https://doi.org/10.1002/path.2987. |
| [72] | Mehta N, Kalra A, Nowacki AS, et al. Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. Published online May 05, 2020. doi: 10.1001/jamacardio.2020.1855. |
| [73] | Reddy R, Asante I, Liu S, et al. Circulating angiotensin peptides levels in Acute Respiratory Distress Syndrome correlate with clinical outcomes: A pilot study. PloS One. 2019; 14 (3): e0213096. Doi: 10.1371/journal.pone.0213096. |
| [74] | M. C. Chappel, C. M. Ferrario, ACE and ACE2: their role to balance the expression of angiotensin II and angiotensin- (1–7), Kidney International, Volume 70, (1), 2006; 8-10. https://doi.org/10.1038/sj.ki.5000321. |
| [75] | Li Y, Cao Y, Zeng Z, et al. Angiotensin-converting enzyme 2/angiotensin- (1-7)/Mas axis prevents lipopolysaccharide-induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF-κB pathways. Sci Rep. 2015; 5:8209. Doi: 10.1038/srep08209. |
| [76] | Vaduganathan M, Vardeny O, Michel T, et al. Renin-Angiotensin-Aldosterone System. Inhibitors in Patients with Covid-19. N Engl J Med 2020; 382:1653-1659 DOI: 10.1056/NEJMsr2005760. |
| [77] | Kuba K, Imai Y, Rao S, et al.: A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 2005; 11: 875–879. |
| [78] | Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Medicine 2020; 46:586–590. |
| [79] | Tikellis C, Thomas MC. Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease. Hindawi Publishing Corporation International Journal of Peptides Volume 2012, 8 pages doi:10.1155/2012/256294. |
| [80] | 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; 1-5 DOI: 10.1002/jmv.25785. |
| [81] | Heurich A, Hofmann-Winkler H, Gierer S, et al. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2014; 88 (2):1293-1307. doi:10.1128/JVI.02202-13. |
| [82] | Haga S, Tsuchiya H, Hirai T, et al. A novel ACE2 activator reduces monocrotaline-induced pulmonary hypertension by suppressing the JAK/STAT and TGF-β cascades with restored caveolin-1 expression. Exp Lung Res. 2015; 41 (1):21-31. doi: 10.3109/01902148.2014.959141. |
| [83] | Li W, Moore M, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature2003; 426, 450–454. https://doi.org/10.1038/nature02145. |
| [84] | Hofmann H, Geier M, Marzi A, et al. Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor. Biochemical and Biophysical Research Communications 2004; 319 (4):1216-1221 https://doi.org/10.1016/j.bbrc.2004.05.114. |
| [85] | Tin-Yun H, Shih-Lu W, Jaw-Chyun C, et al. Design and biological activities of novel inhibitory peptides for SARS-CoV spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Research 2006; 69 (2):70-76. https://doi.org/10.1016/j.antiviral.2005.10.005. |
| [86] | Wong SK, Li W, Moore MJ, Choe H, Farzan M. A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2. The Journal of Biological Chemistry 2004; 279, 3197-3201. Doi: 10.1074/jbc.C300520200. |
| [87] | Mathewson AC, Bishop A, Yao Y, et al. Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2. J Gen Virol. 2008; 89 (Pt11):2741–2745. Doi:10.1099/vir.0.2008/003962-0. |
| [88] | Haga S, Yamamoto N, Nakai-Murakami C, et al. Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry. PNAS 2008; 105 (22): 7809-7814. https://doi.org/10.1073/pnas.0711241105. |
| [89] | Simmons P, Zmora S, Gierer A, Heurich S, Pöhlmann. Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research. Antiviral Res 2013; 100, 605–614. Doi: 10.1016/j.antiviral.2013.09.028. |
| [90] | Millet K, Whittaker GR. Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis. Virus Res 2014; 202:120–134 (2015). doi: 10.1016/j.virusres.2014.11.021. |
| [91] | Yu YT, Chien S, Chen I, et al. Surface vimentin is critical for the cell entry of SARS-CoV. J Biomed Sci 2016; 23, 14. https://doi.org/10.1186/s12929-016-0234-7. |
| [92] | Walls AC, Park YJ, Tortorici MA, et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020; 181 (2): 281–92. https://doi.org/10.1016/j.cell.2020.02.058. |
| [93] | Tai W, He L, Zhang X, et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol 2020; https://doi.org/10.1038/s41423-020-0400-4. |
| [94] | Kai H, Kai M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors—lessons from available evidence and insights into COVID-19. Hypertens Res 2020. https://doi.org/10.1038/s41440-020-0455-8. |
| [95] | Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020. 181 (2): 271-280. e8. https://doi.org/10.1016/j.cell.2020.02.052. |
| [96] | Xu X, Chen P, Wang J, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modelling of its Spike protein for risk of human transmission. Sci China Life Sci 2020; 63, 457–460 (2020). https://doi.org/10.1007/s11427-020-1637-5. |
| [97] | Li F, Li W, Farzan M, Harrison SC. Structure of SARS coronavirus Spike receptor-binding domain complexed with receptor. Science 2005; 309: 1864–1868. |
| [98] | Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol 2020; 94 (7) e00127-20. https://doi.org/10.1128/jvi.00127-20. |
APA Style
Sanjeev Arya, David Maskill, Avinash Sharma, Ankit Khanduri, Prashant Kumar, et al. (2020). Corona Virus (SARS-COV-2) Induced Inflammatory Lung Disease a Review on the Role of Renin–Angiotensin System and the Angiotensin Converting Enzyme-2. American Journal of Internal Medicine, 8(4), 159-171. https://doi.org/10.11648/j.ajim.20200804.14
ACS Style
Sanjeev Arya; David Maskill; Avinash Sharma; Ankit Khanduri; Prashant Kumar, et al. Corona Virus (SARS-COV-2) Induced Inflammatory Lung Disease a Review on the Role of Renin–Angiotensin System and the Angiotensin Converting Enzyme-2. Am. J. Intern. Med. 2020, 8(4), 159-171. doi: 10.11648/j.ajim.20200804.14
AMA Style
Sanjeev Arya, David Maskill, Avinash Sharma, Ankit Khanduri, Prashant Kumar, et al. Corona Virus (SARS-COV-2) Induced Inflammatory Lung Disease a Review on the Role of Renin–Angiotensin System and the Angiotensin Converting Enzyme-2. Am J Intern Med. 2020;8(4):159-171. doi: 10.11648/j.ajim.20200804.14
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.ajim.20200804.14,
author = {Sanjeev Arya and David Maskill and Avinash Sharma and Ankit Khanduri and Prashant Kumar and Dushyant Gaur and Haider Abbas and Sheetal Verma and Vinita Singh},
title = {Corona Virus (SARS-COV-2) Induced Inflammatory Lung Disease a Review on the Role of Renin–Angiotensin System and the Angiotensin Converting Enzyme-2},
journal = {American Journal of Internal Medicine},
volume = {8},
number = {4},
pages = {159-171},
doi = {10.11648/j.ajim.20200804.14},
url = {https://doi.org/10.11648/j.ajim.20200804.14},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20200804.14},
abstract = {In December 2019, a novel infectious disease, caused by Severe Acute Respiratory Syndrome-coronavirus 2 (SARS-CoV-2), was identified in Wuhan, China, now declared as a pandemic. The Renin–Angiotensin system (RAS) and angiotensin-converting enzyme 2 (ACE2) have drawn special attention, as ACE2 acts as a receptor for SARS-CoV2. No specific therapy against SARS-COV2 has been invented yet. There is a constant need towards understanding of the underlying pathophysiology to aid the pharmacological research. We have looked at the current evidence on the relationship between SARS-COV-2 and RAS and ACE2. Articles in English language published between 1st January 2003 and 15th June 2020 were searched using keywords and MeSH (Medical Subject Heading). We used Google Scholar and Pubmed as search engines. Conclusion: Bats serve as primary reservoir for SARS-CoV2, but its intermediate host has not been identified yet. ‘Hot spots’ on ACE2, serve as receptors for SARS-COV2. Imbalance in the activity of ACE/ACE2 is an important contribution towards the pathogenesis of coronavirus related diseases. ACE2 also has protective role and recombinant ACE2 has been shown to improve lung injury and it is a potential therapeutic agent.},
year = {2020}
}
TY - JOUR T1 - Corona Virus (SARS-COV-2) Induced Inflammatory Lung Disease a Review on the Role of Renin–Angiotensin System and the Angiotensin Converting Enzyme-2 AU - Sanjeev Arya AU - David Maskill AU - Avinash Sharma AU - Ankit Khanduri AU - Prashant Kumar AU - Dushyant Gaur AU - Haider Abbas AU - Sheetal Verma AU - Vinita Singh Y1 - 2020/07/17 PY - 2020 N1 - https://doi.org/10.11648/j.ajim.20200804.14 DO - 10.11648/j.ajim.20200804.14 T2 - American Journal of Internal Medicine JF - American Journal of Internal Medicine JO - American Journal of Internal Medicine SP - 159 EP - 171 PB - Science Publishing Group SN - 2330-4324 UR - https://doi.org/10.11648/j.ajim.20200804.14 AB - In December 2019, a novel infectious disease, caused by Severe Acute Respiratory Syndrome-coronavirus 2 (SARS-CoV-2), was identified in Wuhan, China, now declared as a pandemic. The Renin–Angiotensin system (RAS) and angiotensin-converting enzyme 2 (ACE2) have drawn special attention, as ACE2 acts as a receptor for SARS-CoV2. No specific therapy against SARS-COV2 has been invented yet. There is a constant need towards understanding of the underlying pathophysiology to aid the pharmacological research. We have looked at the current evidence on the relationship between SARS-COV-2 and RAS and ACE2. Articles in English language published between 1st January 2003 and 15th June 2020 were searched using keywords and MeSH (Medical Subject Heading). We used Google Scholar and Pubmed as search engines. Conclusion: Bats serve as primary reservoir for SARS-CoV2, but its intermediate host has not been identified yet. ‘Hot spots’ on ACE2, serve as receptors for SARS-COV2. Imbalance in the activity of ACE/ACE2 is an important contribution towards the pathogenesis of coronavirus related diseases. ACE2 also has protective role and recombinant ACE2 has been shown to improve lung injury and it is a potential therapeutic agent. VL - 8 IS - 4 ER -
Email: