Description of cellular receptors in the SARS‐CoV‐2 infectious disease and potential therapeutic approaches

Document Type : Review Paper

Authors

1 Discovery and Translational Research, Biologics Development Sciences, Janssen Biotherapeutics, Spring house, Pennsylvania, USA

2 Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Khyber Pakhtunkhwa, Pakistan

Abstract

SARS-CoV-2 or Covid-19 virus is the cause of severe acute respiratory syndrome. This viral pathogen can infect humans mainly via the tract of respiratory. The virus has an RNA genome that encodes two classes of proteins, including enzymatic and structural proteins. One of the structural peptides placed on the virus surface is the spike protein or S protein. This protein, which appears as a glycoprotein on the surface of the virus, binds the virus to the host cell. This glycoprotein detects and binds to the angiotensin-converting enzyme 2 (ACE2) molecule on the surface of cell. This protein is then processed by a set of proteases of host cell, thus helping the virus entry into the host cell. Protease peptides including TMPRSS2, furin, and cathepsins are contributed to this molecular processing. Therefore, inhibition of any of these receptors could be a promising therapeutic approach for the SARS-CoV-2 treatment. The aim of this study was to define cell receptors in the pathogenicity of Covid-19 virus and to offer probable therapeutic plans based on these receptor’s inhibition.

Graphical Abstract

Description of cellular receptors in the SARS‐CoV‐2 infectious disease and potential therapeutic approaches

Highlights

  • SARS-CoV-2 is the reason of severe acute respiratory syndrome.
  • ACE2, TMPRSS2, furin, and cathepsins cellular receptors contributed to Covid-19 infection.
  • Blocking of cellular receptors could be a promising strategy for SARS-CoV-2 treatment.

Keywords

Main Subjects


1. Keni R, Alexander A, Nayak PG, Mudgal J, Nandakumar K. COVID-19: emergence, spread, possible treatments, and global burden. Front Public Health 2020; 8: 216.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
4. Rehman SU, Shafique L, Ihsan A, Liu Q. Evolutionary trajectory for the emergence of novel coronavirus SARS-CoV-2. Pathogens 2020; 9(3): 240.
5. Wen L, Zhang Y, Yang B, Han F, Ebadi AG, Toughani M. Knockdown of Angiopoietin-like protein 4 suppresses the development of colorectal cancer. Cell Mol Biol 2020; 66(5): 117-124.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed     
6. Mittal A, Manjunath K, Ranjan RK, Kaushik S, Kumar S, Verma V. COVID-19 pandemic: Insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2. PLoS Pathogens 2020; 16(8): e1008762.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
7. Mousavizadeh L, Ghasemi S. Genotype and phenotype of COVID-19: Their roles in pathogenesis. J Microbiol, Immunol Infect 2021; 54(2): 159-163.
8. Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge. Virol J 2019; 16(1): 1-22.
9. Chilamakuri R, Agarwal S. COVID-19: characteristics and therapeutics. Cells 2021; 10(2): 206.
10. Yang M, Abdalrahman H, Sonia U, Mohammed AI, Vestine U, Wang M, Ebadi AG, Toughani M. The application of DNA molecular markers in the study of Codonopsis species genetic variation, a review. Cell Mol Biol 2020; 66(2): 23-30.
12. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, Li T, Chen Q. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci 2020; 12(1): 1-5.
13. Blach S, Kondili LA, Aghemo A, Cai Z, Dugan E, Estes C, Gamkrelidze I, Ma S, Pawlotsky JM, Razavi-Shearer D, Razavi H. Impact of COVID-19 on global HCV elimination efforts. J Hepatol 2021; 74(1): 31-36.
14. Chakaya J, Khan M, Ntoumi F, Aklillu E, Fatima R, Mwaba P, Kapata N, Mfinanga S, Hasnain SE, Katoto PD, Bulabula AN. Global Tuberculosis Report 2020–Reflections on the Global TB burden, treatment and prevention efforts. Int J Infect Dis 2021; 113: S7-
15. Yang M, Shi D, Wang Y, Ebadi AG, Toughani M. Study on Interaction of Coomassie Brilliant Blue G-250 with Bovine Serum Albumin by Multispectroscopic. Int J Peptide Res Therap 2021; 27(1): 421-431.
16. Raj K, Kaur K, Gupta GD, Singh S. Current understanding on molecular drug targets and emerging treatment strategy for novel coronavirus-19. Naunyn-Schmiedeberg's Arch Pharm 2021; 394(7): 1383-1402.
17. Jha NK, Jeyaraman M, Rachamalla M, Ojha S, Dua K, Chellappan DK, Muthu S, Sharma A, Jha SK, Jain R, Jeyaraman N. Current understanding of novel coronavirus: molecular pathogenesis, diagnosis, and treatment approaches. Immuno 2021; 1(1): 30-66.
18. Erok B, Atca Aö. A nonspecific widespread involvement of encephalitis in a Covid-19 patient. Acta Med Mediter 2022; 38(3): 1529.
23. Chao JY, Derespina KR, Herold BC, Goldman DL, Aldrich M, Weingarten J, Ushay HM, Cabana MD, Medar SS. Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 at a Tertiary Care Medical Center in New York City. J Pediatr 2020; 223: 14-19.
24. Harrison AG, Lin T, Wang P. Mechanisms of SARS-CoV-2 Transmission and Pathogenesis. Trends Immunol 2020; 41: 1100-1115.
25. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020; 367(6483): 1260-1263.
26. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020; 181: 281-292.
27. Saleem RT, Butt MH, Ahmad A, Amin M, Amir A, Ahsan A, Fayyaz F, Saleem R, Riaz T, Waheed U, Zaman M. Practices and attitude of self-medication during COVID-19 pandemic in university students with interventional role of pharmacist: a regional analysis. Lat Am J Pharm 2021; 40(8): 1946-1953.
29. Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J, Farzan M, Wohlford-Lenane C, Perlman S, McCray Jr PB. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol 2005; 79(23):14614-14621.
30. Vigerust DJ, Shepherd VL. Virus glycosylation: role in virulence and immune interactions. Trends Microbiol 2007; 15: 211-218.
31. Iffat W, Nesar S, Shakeel S, Qamar A, Nazar S, Rahim M, Tariq AB, Arshad HM. Measures of depressive symptoms using beck depression inventory-ii among healthcare professionals during a pandemic of Covid-19. Lat Am J Pharm 2021; 40(4): 729-734.
32. Yuksel AE, Akinturk N, Dereli O, Anadolu O, Yurtseven T, Derbent A. Our experiences in a neurosurgical operating room during the Covid-19 pandemic. Acta Med Mediter 2022; 38(2): 1061-1064.
CrossRef    Google Scholar    full-text PDF    Mendeley    
33. Lu G, Hu Y, Wang Q, Qi J, Gao F, Li Y, Zhang Y, Zhang W, Yuan Y, Bao J, Zhang B. Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature 2013; 500(7461): 227-231.
34. Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT, Holmes KV. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 1992; 357(6377): 420-422.
35. Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S, Wong SK, Huang IC, Xu K, Vasilieva N, Murakami A. Receptor and viral determinants of SARS‐coronavirus adaptation to human ACE2. EMBO J 2005; 24(8): 1634-1643.
36. Mahmoud MA, Ibrahim AA, Alolayan SO, Bhagavathula AS. A study of public knowledge and pharmacists perceptions of their roles in prevention of COVID-19. Lat Am J Pharm 2021; 40(4): 871-878.
37. Bag HG, Kivrak M, Guldogan E, Colak C. Prediction of covid-19 severity in SARS-COV-2 RNA-positive patients by different ensemble learning strategies. Acta Med Mediter 2022; 38(2): 1085-1091.
38. Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci USA 2009; 106: 5871-5876.
39. Ou T, Mou H, Zhang L, Ojha A, Choe H, Farzan M. Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2. PLoS Pathog 2021; 17: e1009212.
40. Shen LW, Mao HJ, Wu YL, Tanaka Y, Zhang W. TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections. Biochimie 2017; 142: 1-10.
41. Aksakal N, Kocaekşi S, Şen ET, Alp AF, Özbal A, Sabırlı TN, Taşçıoğlu R. A phenomenology study of physical activity before and during Covid-19 lockdown in autistic children. Acta Med Mediter 2022; 38(2): 1229-1235.
42. Chandran K, Sullivan NJ, Felbor U, Whelan SP, Cunningham JM. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science 2005; 308: 1643-5.
43. Batlle D, Wysocki J, Satchell K. Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy? Clin Sci 2020; 134: 543-545.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
45. Liu P, Wysocki J, Souma T, Ye M, Ramirez V, Zhou B, Wilsbacher LD, Quaggin SE, Batlle D, Jin J. Novel ACE2-Fc chimeric fusion provides long-lasting hypertension control and organ protection in mouse models of systemic renin angiotensin system activation. Kidney Int 2018; 94(1): 114-125.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
46. Kayhan S, Kirnap NG. Thyroxin and thyroid-stimulating hormone changes in patients with Covid-19. Acta Med Mediter 2022; 38(1): 431-435.
47. Zoufaly A, Poglitsch M, Aberle JH, Hoepler W, Seitz T, Traugott M, Grieb A, Pawelka E, Laferl H, Wenisch C, Neuhold S. Human recombinant soluble ACE2 in severe COVID-19. Lancet Respirat Med 2020; 8(11): 1154-1158.
49. Chan KK, Dorosky D, Sharma P, Abbasi SA, Dye JM, Kranz DM, Herbert AS, Procko E. Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. Science 2020; 369(6508): 1261-1265.
50. Zhou L, Mao Q, Li J, Huang X, Yu H, Xu X. Analysis of baseline ct findings and evolution of single lesion in the early stage of Covid-19. Acta Med Mediter 2022; 38(1): 473-478.
51. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005; 436(7047): 112-116.
52. Wu J, Deng W, Li S, Yang X. Advances in research on ACE2 as a receptor for 2019-nCoV. Cell Mole life Sci 2021; 78: 531-544.
53. Huentelman MJ, Zubcevic J, Hernández Prada JA, Xiao X, Dimitrov DS, Raizada MK, Ostrov DA. Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor. Hypertension 2004; 44(6): 903-906.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
55. Liu PC, Liu X, Li Y, Covington M, Wynn R, Huber R, Hillman M, Yang G, Ellis D, Marando C, Katiyar K. Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells. Cancer Biol Ther 2006; 5(6): 657-664.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed    
56. Wang S, Guo F, Liu K, Wang H, Rao S, Yang P, Jiang C. Endocytosis of the receptor-binding domain of SARS-CoV spike protein together with virus receptor ACE2. Virus Res 2008; 136(1-2): 8-15.
60. Lucas JM, Heinlein C, Kim T, Hernandez SA, Malik MS, True LD, Morrissey C, Corey E, Montgomery B, Mostaghel E, Clegg N. The Androgen-Regulated Protease TMPRSS2 Activates a Proteolytic Cascade Involving Components of the Tumor Microenvironment and Promotes Prostate Cancer MetastasisTMPRSS2 Influences Prostate Cancer Metastasis. Cancer Discov 2014; 4(11): 1310-1325.
62. Yamamoto M, Matsuyama S, Li X, Takeda M, Kawaguchi Y, Inoue JI, Matsuda Z. Identification of nafamostat as a potent inhibitor of Middle East respiratory syndrome coronavirus S protein-mediated membrane fusion using the split-protein-based cell-cell fusion assay. Antimicrob Agents Chemother 2016; 60(11): 6532-6539.
63. Asakura H, Ogawa H. Potential of heparin and nafamostat combination therapy for COVID-19. J Thromb Haemost 2020; 18: 1521-1522.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed   
65. Hasan A, Paray BA, Hussain A, Qadir FA, Attar F, Aziz FM, et al. A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin. J Biomol Struct Dyn. 2021;39:3025-33.
66. Wu C, Zheng M, Yang Y, Gu X, Yang K, Li M, Liu Y, Zhang Q, Zhang P, Wang Y, Wang Q. Furin: a potential therapeutic target for COVID-19. Iscience 2020; 23(10): 101642.
67. Gianmarco M, Filippo L, Luca C. Cutaneous manifestations among covid-19 affected healthcare workers. Acta Med Mediter 2022; 38(1): 717-723.
68. Rahbar Saadat Y, Hosseiniyan Khatibi SM, Zununi Vahed S, Ardalan M. Host Serine Proteases: A Potential Targeted Therapy for COVID-19 and Influenza. Front Mol Biosci 2021; 8: 725528.
69. Korkmaz B, Lesner A, Marchand-Adam S, Moss C, Jenne DE. Lung Protection by Cathepsin C Inhibition: A New Hope for COVID-19 and ARDS? J Med Chem 2020; 63: 13258-13265.
70. Sahebnasagh A, Saghafi F, Safdari M, Khataminia M, Sadremomtaz A, Talaei Z, Ghaleno HR, Bagheri M, Habtemariam S, Avan R. Neutrophil elastase inhibitor (sivelestat) may be a promising therapeutic option for management of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID-19. J Clin Pharm Therap 2020; 45(6): 1515-1519.
CrossRef    Google Scholar    full-text PDF    Mendeley    PubMed