Generic placeholder image

Current Pharmaceutical Design

Author(s): Hanieh Maleksabet, Elham Rezaee and Sayyed Abbas Tabatabai*

DOI: 10.2174/1381612829666221123111849

DownloadDownload PDF Flyer Cite As
Host-Cell Surface Binding Targets in SARS-CoV-2 for Drug Design

Page: [3583 - 3591] Pages: 9

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a major public health threat to all countries worldwide. SARS-CoV-2 interactions with its receptor are the first step in the invasion of the host cell. The coronavirus spike protein (S) is crucial in binding to receptors on host cells. Additionally, targeting the SARS-CoV-2 viral receptors is considered a therapeutic option in this regard. In this review of literature, we summarized five potential host cell receptors, as host-cell surface bindings, including angiotensin-converting enzyme 2 (ACE2), neuropilin 1 (NRP-1), dipeptidyl peptidase 4 (DPP4), glucose regulated protein-78 (GRP78), and cluster of differentiation 147 (CD147) related to the SARS-CoV-2 infection. Among these targets, ACE2 was recognized as the main SARS-CoV-2 receptor, expressed at a low/moderate level in the human respiratory system, which is also involved in SARS-CoV-2 entrance, so the virus may utilize other secondary receptors. Besides ACE2, CD147 was discovered as a novel SARS-CoV-2 receptor, CD147 appears to be an alternate receptor for SARSCoV- 2 infection. NRP-1, as a single-transmembrane glycoprotein, has been recently found to operate as an entrance factor and enhance SARS Coronavirus 2 (SARS-CoV-2) infection under in-vitro. DPP4, which was discovered as the first gene clustered with ACE2, may serve as a potential SARS-CoV-2 spike protein binding target. GRP78 could be recognized as a secondary receptor for SARS-CoV-2 because it is widely expressed at substantially greater levels, rather than ACE2, in bronchial epithelial cells and the respiratory mucosa. This review highlights recent literature on this topic.

Keywords: SARS-CoV-2, ACE2, COVID-19, neuropilin 1, spike protein, DPP4, GRP78, CD147.

[1]
Bedford J, Enria D, Giesecke J, et al. COVID-19: towards controlling of a pandemic. Lancet 2020; 395(10229): 1015-8.
[http://dx.doi.org/10.1016/S0140-6736(20)30673-5] [PMID: 32197103]
[2]
WHO Middle East Respir Syndr coronavirus (MERS-CoV) WHO. 2020.
[3]
WHO SARS (Severe Acute Respir Syndr WHO. 2020.
[4]
Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17(3): 181-92.
[http://dx.doi.org/10.1038/s41579-018-0118-9] [PMID: 30531947]
[5]
Song Z, Xu Y, Bao L, et al. From SARS to MERS, Thrusting Coronaviruses into the spotlight. Viruses 2019; 11(1): 59.
[http://dx.doi.org/10.3390/v11010059] [PMID: 30646565]
[6]
Wang N, Shi X, Jiang L, et al. Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res 2013; 23(8): 986-93.
[http://dx.doi.org/10.1038/cr.2013.92] [PMID: 23835475]
[7]
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.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[8]
Zhou H, Gao S, Nguyen NN, et al. Stringent homology-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions. Biol Direct 2014; 9(1): 5.
[http://dx.doi.org/10.1186/1745-6150-9-5] [PMID: 24708540]
[9]
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]
[10]
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[11]
Chan CM, Chu H, Wang Y, et al. Carcinoembryonic antigen-related cell adhesion molecule 5 is an important surface attachment factor that facilitates entry of middle east respiratory syndrome coronavirus. J Virol 2016; 90(20): 9114-27.
[http://dx.doi.org/10.1128/JVI.01133-16] [PMID: 27489282]
[12]
Huang Y, Yang C, Xu X, Xu W, Liu S. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 2020; 41(9): 1141-9.
[http://dx.doi.org/10.1038/s41401-020-0485-4] [PMID: 32747721]
[13]
Davies J, Randeva H, Chatha K, et al. Neuropilin-1 as a new potential SARS-CoV-2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID-19. Mol Med Rep 2020; 22(5): 4221-6.
[http://dx.doi.org/10.3892/mmr.2020.11510] [PMID: 33000221]
[14]
Zamorano Cuervo N, Grandvaux N. ACE2: Evidence of role as entry receptor for SARS-CoV-2 and implications in comorbidities. eLife 2020; 9: e61390.
[http://dx.doi.org/10.7554/eLife.61390] [PMID: 33164751]
[15]
Gheblawi M, Wang K, Viveiros A, et al. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system. Circ Res 2020; 126(10): 1456-74.
[http://dx.doi.org/10.1161/CIRCRESAHA.120.317015] [PMID: 32264791]
[16]
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 Med 2020; 46(4): 586-90.
[http://dx.doi.org/10.1007/s00134-020-05985-9] [PMID: 32125455]
[17]
Miyazaki M, Takai S. Tissue angiotensin II generating system by angiotensin-converting enzyme and chymase. J Pharmacol Sci 2006; 100(5): 391-7.
[http://dx.doi.org/10.1254/jphs.CPJ06008X] [PMID: 16799256]
[18]
Gross LZF, Sacerdoti M, Piiper A, Zeuzem S, Leroux AE, Biondi RM. ACE2, the receptor that enables infection by SARS-CoV-2: Biochemistry, structure, allostery and evaluation of the potential development of ACE2 modulators. ChemMedChem 2020; 15(18): 1682-90.
[http://dx.doi.org/10.1002/cmdc.202000368] [PMID: 32663362]
[19]
Kuba K, Imai Y, Penninger JM. Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases. Circ J 2013; 77(2): 301-8.
[http://dx.doi.org/10.1253/circj.CJ-12-1544] [PMID: 23328447]
[20]
Patel VB, Zhong JC, Grant MB, Oudit GY. Role of the ACE2/angiotensin 1–7 axis of the renin–angiotensin system in heart failure. Circ Res 2016; 118(8): 1313-26.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.307708] [PMID: 27081112]
[21]
Turner AJ, Hiscox JA, Hooper NM. ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol Sci 2004; 25(6): 291-4.
[http://dx.doi.org/10.1016/j.tips.2004.04.001] [PMID: 15165741]
[22]
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(8): 875-9.
[http://dx.doi.org/10.1038/nm1267] [PMID: 16007097]
[23]
Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 2000; 275(43): 33238-43.
[http://dx.doi.org/10.1074/jbc.M002615200] [PMID: 10924499]
[24]
Der Sarkissian S, Grobe JL, Yuan L, et al. Cardiac overexpression of angiotensin converting enzyme 2 protects the heart from ischemia-induced pathophysiology. Hypertension 2008; 51(3): 712-8.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.100693] [PMID: 18250366]
[25]
Wong DW, Oudit GY, Reich H, et al. Loss of angiotensin-converting enzyme-2 (Ace2) accelerates diabetic kidney injury. Am J Pathol 2007; 171(2): 438-51.
[http://dx.doi.org/10.2353/ajpath.2007.060977] [PMID: 17600118]
[26]
Rentzsch B, Todiras M, Iliescu R, et al. Transgenic angiotensin- converting enzyme 2 overexpression in vessels of SHRSP rats reduces blood pressure and improves endothelial function. Hypertension 2008; 52(5): 967-73.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.114322] [PMID: 18809792]
[27]
Kuba K, Imai Y, Ohto-Nakanishi T, Penninger JM. Trilogy of ACE2: A peptidase in the renin–angiotensin system, a SARS receptor, and a partner for amino acid transporters. Pharmacol Ther 2010; 128(1): 119-28.
[http://dx.doi.org/10.1016/j.pharmthera.2010.06.003] [PMID: 20599443]
[28]
Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med 2020; 76: 14-20.
[http://dx.doi.org/10.1016/j.ejim.2020.04.037] [PMID: 32336612]
[29]
Meng J, Xiao G, Zhang J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect 2020; 9(1): 757-60.
[http://dx.doi.org/10.1080/22221751.2020.1746200] [PMID: 32228222]
[30]
Zhang P, Zhu L, Cai J, et al. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin ii receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res 2020; 126(12): 1671-81.
[http://dx.doi.org/10.1161/CIRCRESAHA.120.317134] [PMID: 32302265]
[31]
Bornstein SR, Dalan R, Hopkins D, Mingrone G, Boehm BO. Endocrine and metabolic link to coronavirus infection. Nat Rev Endocrinol 2020; 16(6): 297-8.
[http://dx.doi.org/10.1038/s41574-020-0353-9] [PMID: 32242089]
[32]
Khera R, Clark C, Lu Y, Guo Y, Ren S, Truax B, et al. Association of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers with the risk of hospitalization and death in hypertensive patients with coronavirus disease-19. J Am Heart Assoc 2021.
[33]
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]
[34]
Bloch MJ. Renin-angiotensin system blockade in COVID-19. J Am Coll Cardiol 2020; 76(3): 277-9.
[http://dx.doi.org/10.1016/j.jacc.2020.06.003] [PMID: 32674791]
[35]
Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin–angiotensin–aldosterone system inhibitors in patients with COVID-19. N Engl J Med 2020; 382(17): 1653-9.
[http://dx.doi.org/10.1056/NEJMsr2005760] [PMID: 32227760]
[36]
Kreutz R, Algharably EAEH, Azizi M, et al. Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19. Cardiovasc Res 2020; 116(10): 1688-99.
[http://dx.doi.org/10.1093/cvr/cvaa097] [PMID: 32293003]
[37]
Talreja H, Tan J, Dawes M, et al. A consensus statement on the use of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in relation to COVID-19 (corona virus disease 2019). N Z Med J 2020; 133(1512): 85-7.
[PMID: 32242182]
[38]
Stoian AP, Banerjee Y, Rizvi AA, Rizzo M. Diabetes and the COVID-19 pandemic: How insights from recent experience might guide Future management. Metab Syndr Relat Disord 2020; 18(4): 173-5.
[http://dx.doi.org/10.1089/met.2020.0037] [PMID: 32271125]
[39]
Muniyappa R, Gubbi S. COVID-19 pandemic, coronaviruses, and diabetes mellitus. Am J Physiol Endocrinol Metab 2020; 318(5): E736-41.
[http://dx.doi.org/10.1152/ajpendo.00124.2020] [PMID: 32228322]
[40]
Chan KK, Dorosky D, Sharma P, Abbasi SA, Dye JM, Kranz DM, et al. Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. Science 2020; 369(6508): 1261-5.
[41]
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]
[42]
Batlle D, Wysocki J, Satchell K. Soluble angiotensin-converting enzyme 2: A potential approach for coronavirus infection therapy? Clin Sci (Lond) 2020; 134(5): 543-5.
[http://dx.doi.org/10.1042/CS20200163] [PMID: 32167153]
[43]
Li F. Coronavirus spike receptor-binding domain complexed with receptor. Science 2005; 309(5742): 1864-8.
[http://dx.doi.org/10.1126/science.1116480]
[44]
Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426(6965): 450-4.
[http://dx.doi.org/10.1038/nature02145] [PMID: 14647384]
[45]
Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005; 436(7047): 112-6.
[http://dx.doi.org/10.1038/nature03712] [PMID: 16001071]
[46]
Zhang R, Pan Y, Fanelli V, et al. Mechanical stress and the induction of lung fibrosis via the midkine signaling pathway. Am J Respir Crit Care Med 2015; 192(3): 315-23.
[http://dx.doi.org/10.1164/rccm.201412-2326OC] [PMID: 25945397]
[47]
Wösten-van Asperen RM, Lutter R, Specht PA, 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(4): 618-27.
[http://dx.doi.org/10.1002/path.2987] [PMID: 22009550]
[48]
Monteil V, Dyczynski M, Lauschke VM, et al. Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection. EMBO Mol Med 2021; 13(1): e13426.
[http://dx.doi.org/10.15252/emmm.202013426] [PMID: 33179852]
[49]
Khan A, Benthin C, Zeno B, et al. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit Care 2017; 21(1): 234.
[http://dx.doi.org/10.1186/s13054-017-1823-x] [PMID: 28877748]
[50]
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]
[51]
Wang K, Chen W, Zhang Z, et al. CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal Transduct Target Ther 2020; 5(1): 283.
[http://dx.doi.org/10.1038/s41392-020-00426-x] [PMID: 33277466]
[52]
Cui J, Huang W, Wu B, et al. N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin β1 and promotes HCC metastasis. J Pathol 2018; 245(1): 41-52.
[http://dx.doi.org/10.1002/path.5054] [PMID: 29431199]
[53]
Castro APV, Carvalho TMU, Moussatché N, Damaso CRA. Redistribution of cyclophilin A to viral factories during vaccinia virus infection and its incorporation into mature particles. J Virol 2003; 77(16): 9052-68.
[http://dx.doi.org/10.1128/JVI.77.16.9052-9068.2003] [PMID: 12885921]
[54]
Huang Q, Li J, Xing J, et al. CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting the p53-dependent signaling pathway. J Hepatol 2014; 61(4): 859-66.
[http://dx.doi.org/10.1016/j.jhep.2014.04.035] [PMID: 24801417]
[55]
Zhang MY, Zhang Y, Wu XD, et al. Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum. Blood 2018; 131(10): 1111-21.
[http://dx.doi.org/10.1182/blood-2017-08-802918] [PMID: 29352039]
[56]
Lu M, Wu J, Hao ZW, et al. Basolateral CD147 induces hepatocyte polarity loss by E-cadherin ubiquitination and degradation in hepatocellular carcinoma progress. Hepatology 2018; 68(1): 317-32.
[http://dx.doi.org/10.1002/hep.29798] [PMID: 29356040]
[57]
Zhao P, Zhang W, Wang SJ, et al. HAb18G/CD147 promotes cell motility by regulating annexin II-activated RhoA and Rac1 signaling pathways in hepatocellular carcinoma cells. Hepatology 2011; 54(6): 2012-24.
[http://dx.doi.org/10.1002/hep.24592] [PMID: 21809360]
[58]
Su H, Yang Y. The roles of CyPA and CD147 in cardiac remodelling. Exp Mol Pathol 2018; 104(3): 222-6.
[http://dx.doi.org/10.1016/j.yexmp.2018.05.001] [PMID: 29772453]
[59]
Kosugi T, Maeda K, Sato W, Maruyama S, Kadomatsu K. CD147 (EMMPRIN/Basigin) in kidney diseases: from an inflammation and immune system viewpoint. Nephrol Dial Transplant 2015; 30(7): 1097-103.
[http://dx.doi.org/10.1093/ndt/gfu302] [PMID: 25248362]
[60]
Chen Z, Mi L, Xu J, et al. Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus. J Infect Dis 2005; 191(5): 755-60.
[http://dx.doi.org/10.1086/427811] [PMID: 15688292]
[61]
Ulrich H, Pillat MM. CD147 as a target for COVID-19 treatment: Suggested effects of azithromycin and stem cell engagement. Stem Cell Rev Rep 2020; 16(3): 434-40.
[http://dx.doi.org/10.1007/s12015-020-09976-7] [PMID: 32307653]
[62]
Zhai Y, Wu B, Li J, Yao X, Zhu P, Chen Z. CD147 promotes IKK/IκB/NF-κB pathway to resist TNF-induced apoptosis in rheumatoid arthritis synovial fibroblasts. J Mol Med (Berl) 2016; 94(1): 71-82.
[http://dx.doi.org/10.1007/s00109-015-1334-7] [PMID: 26296700]
[63]
Su H, Li J, Chen T, et al. Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway. Mol Cell Biochem 2016; 422(1-2): 85-95.
[http://dx.doi.org/10.1007/s11010-016-2808-9] [PMID: 27590243]
[64]
de Farias T da SM. Melatonin supplementation attenuates the pro-inflammatory adipokines expression in visceral fat from obese mice induced by a high-fat diet. Cells 2019; 8(9): 1041.
[65]
Liu C, von Brunn A, Zhu D. Cyclophilin A and CD147: novel therapeutic targets for the treatment of COVID-19. Med Drug Discov 2020; 7: 100056.
[66]
Leonardi A, Rosani U, Brun P. Ocular surface expression of SARS-CoV-2 receptors. Ocul Immunol Inflamm 2020; 28(5): 735-8.
[http://dx.doi.org/10.1080/09273948.2020.1772314] [PMID: 32589459]
[67]
Aguiar JA, Tremblay BJM, Mansfield MJ, et al. Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue. Eur Respir J 2020; 56(3): 2001123.
[http://dx.doi.org/10.1183/13993003.01123-2020] [PMID: 32675206]
[68]
Radzikowska U, Ding M, Tan G, et al. Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors. Allergy 2020; 75(11): 2829-45.
[http://dx.doi.org/10.1111/all.14429] [PMID: 32496587]
[69]
Jobe A, Vijayan R. Neuropilins: C-end rule peptides and their association with nociception and COVID-19. Comput Struct Biotechnol J 2021; 19: 1889-95.
[http://dx.doi.org/10.1016/j.csbj.2021.03.025] [PMID: 33815686]
[70]
Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science (80-) 2020; 370(6518): 856-60.
[71]
Daly JL, Simonetti B, Klein K, Chen K-E, Williamson MK, Antón-Plágaro C, et al. Neuropilin-1 is a host factor for SARS-CoV- 2 infection. Science 2020; 370(6518): 861-5.
[72]
Gudowska-Sawczuk M, Mroczko B. The role of neuropilin-1 (NRP-1) in SARS-CoV-2 infection. J Clin Med 2021; 10(13): 2772-30.
[http://dx.doi.org/10.3390/jcm10132772] [PMID: 34202613]
[73]
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 2020; 9(11): 2343.
[http://dx.doi.org/10.3390/cells9112343] [PMID: 33105869]
[74]
Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res 2020; 176: 104742.
[http://dx.doi.org/10.1016/j.antiviral.2020.104742] [PMID: 32057769]
[75]
Teesalu T, Sugahara KN, Kotamraju VR, Ruoslahti E. C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc Natl Acad Sci USA 2009; 106(38): 16157-62.
[http://dx.doi.org/10.1073/pnas.0908201106] [PMID: 19805273]
[76]
Murgolo N, Therien AG, Howell B, Klein D, Koeplinger K, Lieberman LA, et al. SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development. PLOS Pathog 2021; 17(2): e1009225.
[77]
Kielian M. Enhancing host cell infection by SARS-CoV-2. Science 2020; 370(6518): 765-6.
[78]
Boesveldt S, Postma EM, Boak D, et al. Anosmia-A Clinical Review. Chem Senses 2017; 42(7): 513-23.
[http://dx.doi.org/10.1093/chemse/bjx025] [PMID: 28531300]
[79]
Ramani A, Müller L, Ostermann PN, et al. SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J 2020; 39(20): e106230.
[http://dx.doi.org/10.15252/embj.2020106230] [PMID: 32876341]
[80]
Mayi BS, Leibowitz JA, Woods AT, Ammon KA, Liu AE, Raja A. The role of Neuropilin-1 in COVID-19. PLoS Pathog 2021; 17(1): e1009153.
[http://dx.doi.org/10.1371/journal.ppat.1009153] [PMID: 33395426]
[81]
Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun 2020; 526(1): 135-40.
[http://dx.doi.org/10.1016/j.bbrc.2020.03.044] [PMID: 32199615]
[82]
Singh A, Singh R. Dipeptidyl-peptidase-4 inhibitors in type 2 diabetes and COVID-19: From a potential repurposed agent to a useful treatment option. Journal of Diabetology 2020; 11(3): 131.
[http://dx.doi.org/10.4103/JOD.JOD_53_20]
[83]
Dalan R. Is DPP4 inhibition a comrade or adversary in COVID-19 infection. Diabetes Res Clin Pract 2020; 164: 108216.
[http://dx.doi.org/10.1016/j.diabres.2020.108216] [PMID: 32416120]
[84]
Scheen AJ, Marre M, Thivolet C. Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports. Diabetes Metab 2020; 46(4): 265-71.
[http://dx.doi.org/10.1016/j.diabet.2020.05.008] [PMID: 32447101]
[85]
Stoian AP, Papanas N, Prazny M, Rizvi AA, Rizzo M. Incretin-based therapies role in COVID-19 era: Evolving insights. J Cardiovasc Pharmacol Ther 2020; 25(6): 494-6.
[http://dx.doi.org/10.1177/1074248420937868] [PMID: 32618198]
[86]
Klemann C, Wagner L, Stephan M, von Hörsten S. Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system. Clin Exp Immunol 2016; 185(1): 1-21.
[http://dx.doi.org/10.1111/cei.12781] [PMID: 26919392]
[87]
Deacon CF. Physiology and pharmacology of DPP-4 in glucose homeostasis and the treatment of type 2 diabetes. Front Endocrinol 2019; 10
[88]
Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012; 33(2): 187-215.
[http://dx.doi.org/10.1210/er.2011-1052] [PMID: 22323472]
[89]
Scheen AJ. Cardiovascular effects of gliptins. Nat Rev Cardiol 2013; 10(2): 73-84.
[http://dx.doi.org/10.1038/nrcardio.2012.183] [PMID: 23296071]
[90]
Raj VS, Mou H, Smits SL, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013; 495(7440): 251-4.
[http://dx.doi.org/10.1038/nature12005] [PMID: 23486063]
[91]
Vankadari N, Wilce JA. Emerging COVID-19 coronavirus: Glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microbes Infect 2020; 9(1): 601-4.
[http://dx.doi.org/10.1080/22221751.2020.1739565] [PMID: 32178593]
[92]
Sesti G, Avogaro A, Belcastro S, et al. Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. Acta Diabetol 2019; 56(6): 605-17.
[http://dx.doi.org/10.1007/s00592-018-1271-3] [PMID: 30603867]
[93]
Norouzi M, Norouzi S, Ruggiero A, et al. Type-2 diabetes as a risk factor for severe COVID-19 infection. Microorganisms 2021; 9(6): 1211.
[http://dx.doi.org/10.3390/microorganisms9061211] [PMID: 34205044]
[94]
Scheen AJ. DPP-4 inhibition and COVID-19: From initial concerns to recent expectations. Diabetes Metab 2021; 47(2): 101213.
[http://dx.doi.org/10.1016/j.diabet.2020.11.005] [PMID: 33249199]
[95]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[96]
Vaninov N. In the eye of the COVID-19 cytokine storm. Nat Rev Immunol 2020; 20(5): 277.
[http://dx.doi.org/10.1038/s41577-020-0305-6] [PMID: 32249847]
[97]
Kagal UA, Angadi NB, Matule SM. Effect of dipeptidyl peptidase 4 inhibitors on acute and subacute models of inflammation in male Wistar rats: An experimental study. Int J Appl basic Med Res 7(1): 26-31.
[98]
Birnbaum Y, Bajaj M, Qian J, Ye Y. Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3/ASC inflammasome. BMJ Open Diabetes Res Care 2016; 4(1): e000227.
[http://dx.doi.org/10.1136/bmjdrc-2016-000227] [PMID: 27547413]
[99]
Mozafari N, Azadi S, Mehdi-Alamdarlou S, Ashrafi H, Azadi A. Inflammation: A bridge between diabetes and COVID-19, and possible management with sitagliptin. Med Hypotheses 2020; 143: 110111.
[http://dx.doi.org/10.1016/j.mehy.2020.110111] [PMID: 32721805]
[100]
Dastan F, Abedini A, Shahabi S, Kiani A, Saffaei A, Zare A. Sitagliptin repositioning in SARS-CoV-2: Effects on ACE-2, CD-26, and inflammatory cytokine storms in the lung. Iran J Allergy Asthma Immunol 2020; 19(S1): 10-2.
[http://dx.doi.org/10.18502/ijaai.v19i(s1.r1).2849] [PMID: 32534505]
[101]
Bonora BM, Avogaro A, Fadini GP. Disentangling conflicting evidence on DPP-4 inhibitors and outcomes of COVID-19: Narrative review and meta-analysis. J Endocrinol Invest 2021; 44(7): 1379-86.
[http://dx.doi.org/10.1007/s40618-021-01515-6] [PMID: 33512688]
[102]
Tomovic K, Lazarevic J, Kocic G, Deljanin-Ilic M, Anderluh M, Smelcerovic A. Mechanisms and pathways of anti-inflammatory activity of DPP-4 inhibitors in cardiovascular and renal protection. Med Res Rev 2019; 39(1): 404-22.
[http://dx.doi.org/10.1002/med.21513] [PMID: 29806214]
[103]
Zhu L, She ZG, Cheng X, et al. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab 2020; 31(6): 1068-1077.e3.
[http://dx.doi.org/10.1016/j.cmet.2020.04.021] [PMID: 32369736]
[104]
Fagerberg L, Hallström BM, Oksvold P, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics 2014; 13(2): 397-406.
[http://dx.doi.org/10.1074/mcp.M113.035600] [PMID: 24309898]
[105]
Li J, Lee A. Stress induction of GRP78/BiP and its role in cancer. Curr Mol Med 2006; 6(1): 45-54.
[http://dx.doi.org/10.2174/156652406775574523] [PMID: 16472112]
[106]
Quinones QJ, de Ridder GG, Pizzo SV. GRP78: a chaperone with diverse roles beyond the endoplasmic reticulum. Histol Histopathol 2008; 23(11): 1409-16.
[PMID: 18785123]
[107]
Lee AS. The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 2005; 35(4): 373-81.
[http://dx.doi.org/10.1016/j.ymeth.2004.10.010] [PMID: 15804610]
[108]
Rao RV, Peel A, Logvinova A, et al. Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett 2002; 514(2-3): 122-8.
[http://dx.doi.org/10.1016/S0014-5793(02)02289-5] [PMID: 11943137]
[109]
Lee AS. Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential. Nat Rev Cancer 2014; 14(4): 263-76.
[http://dx.doi.org/10.1038/nrc3701] [PMID: 24658275]
[110]
Ge R, Kao C. Cell surface GRP78 as a death receptor and an anticancer drug target. Cancers 2019; 11(11): 1787.
[http://dx.doi.org/10.3390/cancers11111787] [PMID: 31766302]
[111]
Rangel HR, Ortega JT, Maksoud S, Pujol FH, Serrano ML. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19 The COVID-19 resource centre is hosted on Elsevier connect, the company’s public news and information. 2020.
[112]
Ibrahim IM, Abdelmalek DH, Elfiky AA. GRP78: A cell’s response to stress. Life Sci 2019; 226: 156-63.
[http://dx.doi.org/10.1016/j.lfs.2019.04.022] [PMID: 30978349]
[113]
Ibrahim IM, Abdelmalek DH, Elshahat ME, Elfiky AA. COVID-19 spike-host cell receptor GRP78 binding site prediction. J Infect 2020; 80(5): 554-62.
[http://dx.doi.org/10.1016/j.jinf.2020.02.026] [PMID: 32169481]
[114]
Carlos AJ, Ha DP, Yeh D-W, Van Krieken R, Gill P, Machida K, et al. GRP78 binds SARS-CoV-2 spike protein and ACE2 and GRP78 depleting antibody blocks viral entry and infection in vitro. BioRxiv 2021; 2021.01.20.427368.
[http://dx.doi.org/10.1101/2021.01.20.427368]
[115]
Wang S, Qiu Z, Hou Y, et al. AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells. Cell Res 2021; 31(2): 126-40.
[http://dx.doi.org/10.1038/s41422-020-00460-y] [PMID: 33420426]
[116]
Christianson HC, Belting M. Heparan sulfate proteoglycan as a cell-surface endocytosis receptor. Matrix Biol 2014; 35: 51-5.
[http://dx.doi.org/10.1016/j.matbio.2013.10.004] [PMID: 24145152]
[117]
Clausen TM, Sandoval DR, Spliid CB, et al. SARS-CoV-2 infection depends on cellular heparan sulfate and ACE2. Cell 2020; 183(4): 1043-1057.e15.
[http://dx.doi.org/10.1016/j.cell.2020.09.033] [PMID: 32970989]
[118]
Smits NC, Kurup S, Rops AL, et al. The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease. J Biol Chem 2010; 285(52): 41143-51.
[http://dx.doi.org/10.1074/jbc.M110.153791] [PMID: 20837479]
[119]
Zhou X, Yang G, Guan F. Biological functions and analytical strategies of sialic acids in tumor. Cells 2020; 9(2): 273.
[http://dx.doi.org/10.3390/cells9020273] [PMID: 31979120]
[120]
Li W, Hulswit RJG, Widjaja I, et al. Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein. Proc Natl Acad Sci USA 2017; 114(40): E8508-17.
[http://dx.doi.org/10.1073/pnas.1712592114] [PMID: 28923942]
[121]
Nguyen L, McCord KA, Bui DT, et al. Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2. Nat Chem Biol 2022; 18(1): 81-90.
[http://dx.doi.org/10.1038/s41589-021-00924-1] [PMID: 34754101]