Dinamika Interaksi Reseptor ACE2 dan SARS-CoV-2 Terhadap Manifestasi Klinis COVID-19

  • Risma Ikawaty Fakultas Kedokteran Universitas Surabaya
Abstract Views: 4593 times
PDF Downloads: 11041 times
Keywords: Coronavirus Disease 19, manifestasi klinis, reseptor ACE2, SARS-CoV-2, variasi genetik, genetic variation, clinical manifestation, ACE2 receptor

Abstract

AbstractBackground: A human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be responsible for coronavirus disease 2019 (COVID-19). Pulmonary complications has been considered as the classical clinical manifestations until symptoms on the extra-pulmonary organs may also occur recently, which might be linked to the presence of angiotensin-converting enzyme 2 (ACE2) receptor. Objective: This article evaluates clinical manifestation of COVID-19 and the presence of ACE2 receptor by looking at its interaction to SARS-CoV-2. Methods: 27 articles in English have been selected through search engine PubMed and Google Scholar by using specific keywords. These articles include research journals, case report, systematic review and meta-analysis, and textbooks. Result: Pathogenesis of COVID-19 begins with the binding of spike protein SARS-CoV-2 to ACE2 receptor of host cells. Clinical manifestation of COVID-19 is no longer limited to the pulmonary system but also extra-pulmonary systems since ACE2 receptor abundantly distributed on the other organs. Further, genetic variations of region binding protein of viral spike protein and ACE2 receptor may predispose clinical manifestation of COVID19.  Conclusions: Dynamic interplay between SARS-CoV-2 and receptor ACE2 has great implication to the clinical symptoms. Genetic variation of spike protein SARS-CoV-2 play role not only for cross transmission but also its virulence, while genetic variation of human receptor ACE2 influences its susceptibility or resistance against the infection.

Keywords: ACE2 receptor, Coronavirus Diseases-19, clinical manifestation, SARS-CoV-2, genetic variation.

Abstrak— Virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) merupakan penyebab utama dari coronavirus disease 2019 (COVID-19). Komplikasi pernapasan diangap sebagai gejala klinis klasik hingga akhirnya timbul berbagai manifestasi klinis di organ lain sebagai gejala awal COVID19. Hal ini kemudian dihubungkan dengan reseptor angiotensin-converting enzyme 2 (ACE2). Artikel ini mengevaluasi manifestasi klinis yang disebabkan  interaksi antara reseptor ACE2 dan SARS-CoV-2. PubMed dan Google Scholar digunakan untuk mencari artikel dengan kata kunci yang spesifik untuk COVID-19, SARS-CoV-2, reseptor ACE2, variasi genetik, dan manifestasi klinisnya. Dua puluh tujuh artikel berbahasa Inggris yang digunakan termasuk jurnal penelitian, laporan kasus, systematic review, meta-analysis, dan buku teks. Patogenesis COVID19 dimulai dengan ikatan protein Spike SARS-CoV-2 dan reseptor ACE2. Studi memperlihatkan bahwa reseptor ACE2 ditemui di berbagai jaringan/organ selain organ sistem respirasi sehingga memperlihatkan gejala klinis yang berbeda. Selain itu variasi genetik yang terdapat pada protein spike dari virus dan reseptor ACE2 juga merupakan faktor penting pada terjadinya COVID19. Penulis menyimpulkanbahwa dinamika interaksi antara reseptor ACE2 dan protein spike SARS-CoV-2 termasuk variasi genetic, keduanya memegang peranan penting terhadap suseptibilitas/resistensi dan manifestasi klinis COVID19.

Kata kunci: Coronavirus Diseases-19, manifestasi klinis,  reseptor ACE2, SARS-CoV-2, variasi genetik.

Downloads

Download data is not yet available.

References

  1. Tu YF, Chien CS, Yarmishyn AA, Lin YY, Luo YH, Lin YT, et al. A review of sars-cov-2 and the ongoing clinical trials. Int J Mol Sci. 2020;21(7).


  2. Bourgonje AR, Abdulle AE, Timens W, Hillebrands J. Angiotensin-converting enzyme-2 (ACE2), SARS-CoV-2 and pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol. 2020;


  3. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11(8):875–9.


  4. Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J, et al. ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human Airway Epithelia. J Virol. 2005;79(23):14614–21.


  5. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–7.


  6. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;92(6):552–5.


  7. Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020;11.


  8. Yeager A. Lost Smell and Taste Hint COVID-19 Can Target the Nervous System. The Scientist Magazine. 2020;


  9. Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, et al. Features of anosmia in COVID-19. Med Mal Infect [Internet]. 2020;4–7. Available from: https://doi.org/10.1016/j.medmal.2020.04.006


  10. Wu P, Duan F, Luo C, Liu Q, Qu X, Liang L, et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. 2020;138(5):575–8.


  11. Loon SC, Teoh SCB, Oon LLE, Se-Thoe SY, Ling AE, Leo YS, et al. The severe acute respiratory syndrome coronavirus in tears. Br J Ophthalmol. 2004;88(7):861–3.


  12. Man X, Hongda Z, Xiaoguang N. COVID-19 patient firstly visiting eye doctor due to tarsadenitis and subconjunctival hemorrhage : A case report. Chinese J Exp Ophthalmol. 2020;(04).


  13. Su H, Yang M, Wan C, Yi LX, Tang F, Zhu HY, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int [Internet]. 2020; Available from:https://doi.org/10.1016/j.kint.2020.04.003


  14. Cheung KS, Hung IF, Chan PP, Lung KC, Tso E, Liu R, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis. Gastroenterology [Internet]. 2020; Available from: https://doi.org/10.1053/j.gastro.2020.03.065


  15. Long B, Brady WJ, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. Am J Emerg Med [Internet]. 2020;4–7. Available from: https://doi.org/10.1016/j.ajem.2020.04.048


  16. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. 2020;


  17. Muus C, Luecken MD, Eraslan G, Waghray A, Heimberg G, Sikkema L, et al. Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells. bioRxiv. 2020;


  18. Baraniuk C. Receptors for SARS-CoV-2 Present in Wide Variety of Human Cells. The Scientist Magazine. 2020 Apr;


  19. Black JG, Black LJ. Microbiology Principles and Explorations. 9th ed. Wiley; 2015.


  20. Tortora GJ, Funke BR, Case CL. Microbiology an Introduction. 12th ed. Pearson; 2016. 390–419 p.


  21. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen 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.


  22. Magrone T, Magrone M, Jirillo E. Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective. Endocr Metab Immune Disord Drug Targets. 2020;20(00):1–5.


  23. Li F, Li W, Farzan M, Harrison SC. Structural biology: Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science (80- ). 2005;309(5742):1864–8.


  24. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020;63(3):457–60.


  25. Luo Y, Liu C, Guan T, Li Y, Lai Y, Li F, et al. Association of ACE2 genetic polymorphisms with hypertension-related target organ damages in south Xinjiang. Hypertens Res [Internet]. 2019;42(5):681–9. Available from: http://dx.doi.org/10.1038/s41440-018-0166-6


  26. Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov [Internet]. 2020;6(1):4–7. Available from: http://dx.doi.org/10.1038/s41421-020-0147-1


  27. Hussain M, Jabeen N, Raza F, Shabbir S, Baig AA, Amanullah A, et al. Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein. J Med Virol. 2020;(January).


Published
2020-06-26
How to Cite
Ikawaty, R. (2020). Dinamika Interaksi Reseptor ACE2 dan SARS-CoV-2 Terhadap Manifestasi Klinis COVID-19. Keluwih: Jurnal Kesehatan Dan Kedokteran, 1(2), 67-73. https://doi.org/10.24123/kesdok.V1i2.2869