Spike protein of the SARS-CoV-2 virus and its relationship with the angiotensin-converting enzyme-2
Keywords:
COVID-19, SARS-CoV-2, spike protein, angiotensin converting enzyme 2, vaccinesAbstract
Introduction: COVID-19 caused by the SARS-CoV-2 virus is a pandemic that has claimed the lives of millions of people and overloaded health services around the world.
Objective: to describe the relationship between the spike protein (S) of SARS-CoV-2 and the angiotensin-converting enzyme 2 as the primary trigger of COVID-19 infection.
Method: a bibliographic search was carried out in Google Scholar, SciELO and PubMed, with the initial descriptors COVID-19 and SARS-CoV-2. The publication period selected was between the years 2019 to 2021, without restrictions regarding the type of article. The papers had to be available in full text in Spanish and English.
Results: the spike protein of SARS-CoV-2, which plays a key role in receptor recognition and in the cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain (RBD) that binds to the host's receptor, angiotensin-converting enzyme 2, while the S2 subunit is involved in the viral and cellular membrane fusion. The tissue ubiquity of angiotensin converting enzyme 2 explains the multiple clinical manifestations of the disease.
Conclusions: the knowledge of the relationship between SARS-CoV-2 and its receptor the angiotensin-converting enzyme 2, allows not only to know the pathophysiology of COVID-19, but also the design of antiviral drugs and vaccines that contribute to the prevention and treatment of this viral disease.
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References
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22. Suzuki YJ, Gychka SG. Sars-cov-2 spike protein elicits cell signaling in human host cells: Implications for possible consequences of covid-19 vaccines. Vaccines [Internet]. 2021 [citado 20 May 2021]; 9(1):1-8. DOI: https://doi.org/10.3390/vaccines9010036
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24. Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol [Internet]. 2020 [citado 20 May 2021]; 92(6):595-601. DOI: https://doi.org/10.1002/jmv.25726
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26. Loganathan S, Kuppusamy M, Wankhar W, Gurugubelli KR, Mahadevappa VH, Lepcha L, et al. Angiotensin-converting enzyme 2 (ACE2): COVID 19 gate way to multiple organ failure syndromes. Resp Physiol Neurobiol [Internet]. 2021 [citado 20 May 2021]; 283:103548. DOI: https://doi.org/10.1016/j.resp.2020.103548
27. Arandia-Guzmán J, Antezana-Llaveta G. SARS-CoV-2: estructura, replicación y mecanismos fisiopatológicos relacionados con COVID-19. Gac Med Bol [Internet]. 2020 [citado 20 May 2021]; 43(2):170-178. Disponible en: http://www.scielo.org.bo/scielo.php?script=sci_arttext&pid=S1012-29662020000200009&lng=es
28. Díaz PLA, Espino EA. Manifestaciones gastrointestinales de pacientes infectados con el nuevo Coronavirus SARS-CoV-2. Rev Gastroenterol Latinoam [Internet]. 2020 [citado 24 Jun 2021]; 31(1):35-38. Disponible en: https://gastrolat.org/DOI/PDF/10.46613/gastrolat202001-05.pdf
29. Steardo L, Steardo LJ, Zorec R, Verkhratsky A. Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19. Acta Physiol [Internet]. 2020 [citado 20 May 2021]; 229(3):10-13. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228251
30. Rodríguez MD, Luis León C. Similitudes y diferencias entre el síndrome respiratorio agudo severo causado por SARS-CoV y la COVID-19. Rev Cubana Ped [Internet]. 2020 [citado 20 May 2021]; 92(Supl. especial):e1223. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0034-75312020000500014
31. Carod-Artal FJ. Complicaciones neurológicas por coronavirus y COVID-19. Rev Neurol [Internet]. 2020 [citado 20 May 2021]; 70(9):311-322. Disponible en: https://www.neurologia.com/articulo/2020179
32. Noria SA, Bachini JP, Ramos MV. Coronavirus and cardiovascular system. Rev Urug Cardiol [Internet]. 2020 [citado 26 May 2021]; 35(2):193-208. DOI: http://dx.doi.org/10.29277/cardio.35.2.13
33. Tan W, Aboulhosn J. The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease. Int J Cardiol [Internet]. 2020 [citado 26 May 2021]; 309:70-77. DOI: https://doi.org/10.1016/j.ijcard.2020.03.063
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35. Jia Z, Gong W. Will Mutations in the Spike Protein of SARS-CoV-2 Lead to the Failure of COVID-19 Vaccines? J Korean Med Sci [Internet]. 2021 [citado 26 May 2021]; 36(18): e124. DOI: https://doi.org/10.3346/jkms.2021.36.e124
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40. Sharma A, AhmadFarouk I, Lal SK. COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention. Viruses [Internet]. 2021 [citado 26 May 2021]; 13:202. DOI: https://doi.org/10.3390/v13020202
2. Domínguez L, Amador-Bedolla C. El origen de COVID-19: lo que se sabe, lo que se supone y (muy poquito). Educ Quim [Internet]. 2020 [citado 24 Jun 2021]; 31(2):3-11. DOI: https://doi.org/10.22201/fq.l8708404e.2020.2.75461
3. Xia X. Domains and functions of spike protein in sars-cov-2 in the context of vaccine design. Viruses [Internet]. 2021 [citado 24 Jun 2021]; 13(1):1-16. Disponible en: https://www.mdpi.com/1999-4915/13/1/109/htm
4. Sternberg A, Naujokat C. Structural features of coronavirus SARS-CoV-2 spike protein: Targets for vaccination. Life Sci [Internet]. 2020 [citado 24 Jun 2021]; 257:1-7. DOI: https://doi.org/10.1016/j.lfs.2020.118056
5. Vásquez Moctezuma I. La glucoproteína spike. Rev Mex Mastol [Internet]. 2021 [citado 24 Jun 2021]; 11(1):18–21. Disponible en: https://www.medigraphic.com/pdfs/revmexmastol/ma-2021/ma211c.pdf
6. Bian J, Li Z. Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator. Acta Phar Sin B [Internet]. 2021 [citado 24 Jun 2021]; 11(1):1-12. DOI: https://doi.org/10.1016/j.apsb.2020.10.006
7. Montaño LM, Flores-soto E. COVID-19 y su asociación con los inhibidores de la enzima convertidora de angiotensina y los antagonistas de los receptores para angiotensina II. Rev Fac Med UNAM [Internet]. 2020 [citado 24 Jun 2021]; 63(4):30-34. DOI: http://doi.org/10.22201/fm.24484865e.2020.63.4.05
8. Urrea GSA. Fisiopatología de COVID-19: función del receptor ACE2 y su vínculo con el ejercicio físico de moderada intensidad. Kinesiologia [Internet]. 2020 [citado 24 Jun 2021]; 39(1):26-31. Disponible en: https://drive.google.com/file/d/1DpjgPR3V9QiiPxxNbSg8snI9YqNz7Ond/view
9. Cano F, Gajardo M, Freundlich M. Renin Angiotensin Axis, Angiotensin Converting Enzyme 2 and Coronavirus. Rev Chil Ped [Internet]. 2020 [citado 24 Jun 2021]; 91(3):330-338. DOI: http://dx.doi.org/10.32641/rchped.vi91i3.2548
10. Alcocer-Díaz-Barreiro L, Cossio-Aranda J, Verdejo-Paris J, Odin-De-los-ríos M, Galván-Oseguera H, Álvarez-López H, et al. COVID-19 y el sistema renina, angiotensina, aldosterona. Una relación compleja. Arch Cardiol Mex [Internet]. 2020 [citado 24 Jun 2021]; 90:19-25. Disponible en: http://www.scielo.org.mx/pdf/acm/v90s1/1405-9940-ACM-90-Supl-19.pdf
11. Ortiz Sablón JC, Chacón Bonet D, Serra Hernandez E, Ochoa Tamayo I, Serra Parra Ld, Parra Hijuelo C. Aproximación a la patogenia de la COVID-19 según interacción virus-huésped. CCM [Internet]. 2020 [citado 24 Jun 2021]; 24(3):[aprox. 0 p.]. Disponible en: http://www.revcocmed.sld.cu/index.php/cocmed/article/view/3734
12. Jurado J, Moreno Á, Álvarez J, Polonio B, Martín J, Mohedano A, et al. Aproximación a la virología por coronavirus humanos (HCOV) y fisiopatología de canales iónicos en las células alveolares tipo II pulmonares en Sars-cov y Mers-cov. Salux, Rev Cienc Hum [Internet]. 2020 [citado 24 Jun 2021]; 10:6-9. Disponible en: www.revistasalux.com/app/download/5822918385/SALUX+NUMERO+10+%28Especial+COVID19%29.pdf
13. Sotomayor Lugo F, Corbacho Padilla JM, Valiente Linares AM, Benítez Cordero Y, Viera González T. General aspects about the structure of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Rev Cubana Inv Biom [Internet]. 2020 [citado 24 Jun 2021]; 39(3):e867. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0864-03002020000300025&lng=es
14. Pillay TS. Gene of the month: The 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein. J Clin Pathol [Internet]. 2020 [citado 24 Jun 2021]; 73(7):366-369. Disponible en: https://jcp.bmj.com/content/jclinpath/73/7/366.full.pdf
15. Molina DI, Muñoz TM, Guevara K. Inhibidores de la enzima convertidora de angiotensina y bloqueadores de los receptores de angiotensina II: ¿aumentan el riesgo de padecer COVID-19? Rev Colomb Cardiol [Internet]. 2020 [citado 24 Jun 2021]; 27(3):132-136. DOI: https://doi.org/10.1016/j.rccar.2020.05.003
16. Lu J, Sun PD. High affinity binding of SARS-cov-2 spike protein enhances ACE2 carboxypeptidase activity. J Biol Chem [Internet]. 2020 [citado 24 Jun 2021]; 295(52):18579-18588. DOI: http://dx.doi.org/10.1074/jbc.RA120.015303
17. Papageorgiou AC, Mohsin I. The SARS-CoV-2 Spike Glycoprotein as a Drug and Vaccine Target: Structural Insights into Its Complexes with ACE2 and Antibodies. Cells [Internet]. 2020 [citado 24 Jun 2021]; 9(11). DOI: https://doi.org/10.3390/cells9112343
18. Malik YA. Properties of coronavirus and SARS-CoV-2. Malays J Pathol [Internet]. 2020 [citado 24 Jun 2021]; 42(1):3-11. Disponible en: https://www.proquest.com/openview/1e4a464af43ce070e432ae1a63df64fa/1?pq-origsite=gscholar&cbl=996340
19. Ming Y, Qiang L. Involvement of Spike Protein, Furin, and ACE2 in SARS-CoV-2-Related Cardiovascular Complications. SN Compr Clin Med [Internet]. 2020 [citado 24 Jun 2021]; 2(8). Disponible en: https://link.springer.com/article/10.1007/s42399-020-00400-2
20. Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol J [Internet]. 2020 [citado 20 May 2021]; 215(108427):1-7. DOI: https://doi.org/10.1016/j.clim.2020.108427
21. Huang Y, Yang C, Xu X feng, Xu W, Liu S wen. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin [Internet]. 2020 [citado 20 May 2021]; 41(9):1141-1149. DOI: http://dx.doi.org/10.1038/s41401-020-0485-4
22. Suzuki YJ, Gychka SG. Sars-cov-2 spike protein elicits cell signaling in human host cells: Implications for possible consequences of covid-19 vaccines. Vaccines [Internet]. 2021 [citado 20 May 2021]; 9(1):1-8. DOI: https://doi.org/10.3390/vaccines9010036
23. Pastrian-Soto G. Genetic and Molecular Basis of COVID-19 (SARS-CoV-2) Mechanisms of Pathogenesis and Imnune. Int J Odontostomat [Internet]. 2020 [citado 20 May 2021]; 14(3):331-337. DOI: http://dx.doi.org/10.4067/S0718-381X2020000300331
24. Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol [Internet]. 2020 [citado 20 May 2021]; 92(6):595-601. DOI: https://doi.org/10.1002/jmv.25726
25. Ghafouri-Fard S, Noroozi R, Omrani MD, Branicki W, Pośpiech E, Sayad A, et al. Angiotensin converting enzyme: A review on expression profile and its association with human disorders with special focus on SARS-CoV-2 infection. Vascul Pharmacol [Internet]. 2020 [citado 20 Oct 2021]; 130:106680. DOI: https://doi.org/10.1016/j.vph.2020.106680
26. Loganathan S, Kuppusamy M, Wankhar W, Gurugubelli KR, Mahadevappa VH, Lepcha L, et al. Angiotensin-converting enzyme 2 (ACE2): COVID 19 gate way to multiple organ failure syndromes. Resp Physiol Neurobiol [Internet]. 2021 [citado 20 May 2021]; 283:103548. DOI: https://doi.org/10.1016/j.resp.2020.103548
27. Arandia-Guzmán J, Antezana-Llaveta G. SARS-CoV-2: estructura, replicación y mecanismos fisiopatológicos relacionados con COVID-19. Gac Med Bol [Internet]. 2020 [citado 20 May 2021]; 43(2):170-178. Disponible en: http://www.scielo.org.bo/scielo.php?script=sci_arttext&pid=S1012-29662020000200009&lng=es
28. Díaz PLA, Espino EA. Manifestaciones gastrointestinales de pacientes infectados con el nuevo Coronavirus SARS-CoV-2. Rev Gastroenterol Latinoam [Internet]. 2020 [citado 24 Jun 2021]; 31(1):35-38. Disponible en: https://gastrolat.org/DOI/PDF/10.46613/gastrolat202001-05.pdf
29. Steardo L, Steardo LJ, Zorec R, Verkhratsky A. Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19. Acta Physiol [Internet]. 2020 [citado 20 May 2021]; 229(3):10-13. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228251
30. Rodríguez MD, Luis León C. Similitudes y diferencias entre el síndrome respiratorio agudo severo causado por SARS-CoV y la COVID-19. Rev Cubana Ped [Internet]. 2020 [citado 20 May 2021]; 92(Supl. especial):e1223. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0034-75312020000500014
31. Carod-Artal FJ. Complicaciones neurológicas por coronavirus y COVID-19. Rev Neurol [Internet]. 2020 [citado 20 May 2021]; 70(9):311-322. Disponible en: https://www.neurologia.com/articulo/2020179
32. Noria SA, Bachini JP, Ramos MV. Coronavirus and cardiovascular system. Rev Urug Cardiol [Internet]. 2020 [citado 26 May 2021]; 35(2):193-208. DOI: http://dx.doi.org/10.29277/cardio.35.2.13
33. Tan W, Aboulhosn J. The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease. Int J Cardiol [Internet]. 2020 [citado 26 May 2021]; 309:70-77. DOI: https://doi.org/10.1016/j.ijcard.2020.03.063
34. Chung JY, Thone MN, Kwon YJ.COVID-19 vaccines: The status and perspectives in delivery points of view. Adv Drug Deliv Rev [Internet]. 2021 [citado 26 May 2021]; 170:1-25. DOI: https://doi.org/10.1016/j.addr.2020.12.011
35. Jia Z, Gong W. Will Mutations in the Spike Protein of SARS-CoV-2 Lead to the Failure of COVID-19 Vaccines? J Korean Med Sci [Internet]. 2021 [citado 26 May 2021]; 36(18): e124. DOI: https://doi.org/10.3346/jkms.2021.36.e124
36. Butt AA, Omer SB, Yan P, Shaikh OS, Mayr FB. SARS-CoV-2 vaccine effectiveness in a high-risk national population in a real-world setting. Ann Intern Med [Internet]. 2021 [citado 26 May 2021]. DOI: https://doi.org/10.7326/M21-1577
37. Yaffe H. Las cinco vacunas de Cuba contra el COVID-19: la historia completa sobre Soberana 01/02/Plus, Abdala y Mambisa. LSE Latin America Caribbean Blog [Internet]. 2021 [citado 26 May 2021]. Disponible en: http://eprints.lse.ac.uk/110635/1/latamcaribbean_2021_04_20_las_cinco_vacunas_de_cuba_contra_el_covid.pdf
38. Sharma K, Koirala K, Nicolopoulos K, Chiu C, Wood N, Brittonet PN. Vaccines for COVID-19: Where do we stand in 2021? Paed Resp Rev [Internet]. 2021 Sep [citado 26 May 2021]; 39:22-31. DOI: https://doi.org/10.1016/j.prrv.2021.07.001
39. Dai L, Gao GF. Viral targets for vaccines against COVID-19. Nat Rev Immunol [Internet]. 2021 [citado 26 May 2021]; 21:73-82. DOI: https://doi.org/10.1038/s41577-020-00480-0
40. Sharma A, AhmadFarouk I, Lal SK. COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention. Viruses [Internet]. 2021 [citado 26 May 2021]; 13:202. DOI: https://doi.org/10.3390/v13020202
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2021-10-25
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Díaz-Armas MT, Sánchez-Artigas R, Matute-Respo TZ, Llumiquinga-Achi RA. Spike protein of the SARS-CoV-2 virus and its relationship with the angiotensin-converting enzyme-2. Rev Inf Cient [Internet]. 2021 Oct. 25 [cited 2025 Apr. 18];100(5):e3633. Available from: https://revinfcientifica.sld.cu/index.php/ric/article/view/3633
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