How does Heparan Sulfate and COVID-19 Work?: An Overview
HEPARAN SULFATE IN COVID-19
Abstract
Globally, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) had infected over 3 million individuals and claimed many lives producing a global epidemic that necessitates the rapid development of therapeutic solutions. The ideal technique for quickly deploying well-characterized medicines against novel infections is known as drug repurposing. Several repurposable medicines are currently being tested to see if they may be used to treat COVID-19. Heparin, which is commonly utilized to reduce thrombotic events associated with COVID-19-induced disease, is one such promising drug. Heparansulphate is prevalently expressed in mammalian tissues. CoV-2 requires the helping cofactor heparansulphate (HS) on the cell surface: knocking down genes related in HS formation or treating cells with an HS mimic both prevent spike-mediated viral entrance. Heparin/HS binds directly to spike and promotes viral entrance by facilitating the attachment of spike-bearing viral particles to the cell surface. As documented with cell surface-bound heparansulphate, heparin binding to the open conformation of the spike structurally supports the state and may enhance ACE2 binding. Thus, heparansulphate could potentially be utilised to prevent SARS-CoV-2 transmission, based on available datas also consumption of heparansulphate during SARS-CoV-2 cellular entrance may play a role in the thrombotic events associated with COVID-19 infection. Furthermore, this study provides the findings on the mechanism(s) by which heparansulphate could slow the progression of SARS-CoV-2 infection.
Keywords: COVID-19, HeparanSulphate, Spike Protiens
Keywords:
COVID-19, Heparan Sulphate, Spike ProtiensDOI
https://doi.org/10.22270/jddt.v11i6.5138References
Kinaneh S, Khamaysi I, Karram T, Hamoud S. Heparanase as a potential player in SARS-CoV-2 infection and induced coagulopathy. Biosci Rep.2021 30; 41(7):BSR20210290. 10.1042/BSR20210290
Tandon, R., Sharp, J. S., Zhang, F., Pomin, V. H., Ashpole, N. M., Mitra, D., et al. Effective inhibition of SARS-CoV-2 entry by heparin and enoxaparin derivatives. BioRxiv. 2020:140236.10.1101/2020.06.08.140236
Zhou, B., She, J.Q., Wang, Y.D. and Ma, X.C. Venous thrombosis and arteriosclerosis obliterans of lower extremities in a very severe patient with 2019 novel coronavirus disease: a case report. J. Thromb. Thrombolys. 2020; 50:229–232.10.1007/s11239-020-02084-w
Zhang, Y., Xiao, M., Zhang, S. et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N. Engl. J. Med. 2020; 382:e38. 10.1056/NEJMc2007575
Bikdeli, B., Madhavan, M.V., Jimenez, D. et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotictherapy, and follow-up: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 2020; 75:2950–2973.10.1016/j.jacc.2020.04.031
Wang, Y.D., Zhang, S.P., Wei, Q.Z. et al. COVID-19 complicated with DIC: 2 cases report and literatures review. ZhonghuaXue Ye XueZaZhi. 2020; 41:245–247. 10.3760/cma.j.issn.0253-2727.2020.0001
Yu M, Zhang T, Zhang W, Sun Q, Li H, Li JP. Elucidating the Interactions Between Heparin/Heparan Sulfate and SARS-CoV-2-Related Proteins-An Important Strategy for Developing Novel Therapeutics for the COVID-19 Pandemic. Front MolBiosci. 2021; 25(7):628551.10.3389/fmolb.2020.628551
Guan, W.J., Ni, Z.Y., Hu, Y. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020; 382:1708–1720. 10.1056/NEJMoa2002032
Tang, N., Li, D., Wang, X. and Sun, Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost. 2020; 18:844–847.10.1111/jth.14768
Haraldsson B, Nyström J, Deen WM. Properties of the Glomerular Barrier and Mechanisms of Proteinuria. Physiol Rev.2008; 88(2):451–87.10.1152/physrev.00055.2006
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020; 395(10234):1417–8. 10.1016/S0140-6736(20)30937-5
Sardu C, Gambardella J, Morelli M, Wang X, Marfella R, Santulli G. Is COVID-19 an endothelial disease? Clinical and basic evidence.2020:2020040204.10.20944/preprints202004.0204.v1
Goldberg R, Meirovitz A, Hirshoren N, Bulvik R, Binder A, Rubinstein AM, et al. Versatile role of heparanase in inflammation. Matrix Biol. 2013; 2(5):234–40.10.3389/fonc.2019.00331
Kiyan Y, Tkachuk S, Kurselis K, Shushakova N, Stahl K, Dawodu D, et al.Heparanase-2 protects from LPS-mediated endothelial injury by inhibitingTLR4 signalling. Sci Rep. 2019; 9(1):13591.10.1038/s41598-019-50068-5
Schmidt EP, Yang Y, Janssen WJ, Gandjeva A, Perez MJ, Barthel L, et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med .2012; 18(8):1217–23.10.1038/nm.2843
Goldberg R, Meirovitz A, Hirshoren N, Bulvik R, Binder A, Rubinstein AM, et al. Versatile role of heparanase in inflammation. Matrix Biol. 2013; 32(5):234–40.10.1016/j.matbio.2013.02.008
Wang, L., Brown, J. R., Varki, A., and Esko, J. D. Heparin’s anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectins. J. Clin. Invest. 2002; 110:127–136.10.1172/JCI14996
Lu, L., Liu, Q., Zhu, Y., Chan, K. H., Qin, L., Li, Y., et al. Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor. Nat. Commun.2004; 5:3067.10.1038/ncomms4067
Nadir, Y., Brenner, B., Zetser, A. et al. Heparanase induces tissue factor expression in vascular endothelial and cancer cells. J. Thromb. Haemost.2006; 4:2443–2451.10.1111/j.1538-7836.2006.02212.x
Li JP, Kusche-Gullberg M. Heparan sulfate: biosynthesis, structure, and function. Int Rev Cell Mol Biol. 2016; 325:215–73.10.1016/bs.ircmb.2016.02.009
Cagno V, Tseligka ED, Jones ST, Tapparel C. Heparansulfate proteoglycans and viral attachment: true receptors or adaptation bias? Viruses. 2019; 11(7):11.10.3390/v11070596
Xu, D., and Esko, J. D. Demystifying heparansulfateprotein interactions. Annu. Rev. Biochem. 2014; 83:129–157.10.1146/annurev-biochem-060713-035314
Gallagher, T. M., and Buchmeier, M. J. Coronavirus spike proteins in viral entry and pathogenesis. Virology.2001; 279:371–374.10.1006/viro.2000.0757
Shukla, D. and Spear, P.G. Herpesviruses and heparan sulfate: an intimate relationship in aid of viral entry. J. Clin. Invest.2001; 108:503–510.10.1172/JCI13799
Lang J, Yang N, Deng J, Liu K, Yang P, Zhang G, Jiang C. Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans. PLoS One. 2011; 6(8):e23710. 10.1371/journal.pone.0023710
Nyberg K, Ekblad M, Bergström T, Freeman C, Parish CR, Ferro V, Trybala E. The low molecular weight heparan sulfate-mimetic, PI-88, inhibits cell-to-cell spread of herpes simplex virus. Antiviral Res. 2004; 63(1):15-24. 10.1016/j.antiviral.2004.01.001
Mercer, J.; Schelhaas, M.; Helenius, A. Virus entry by endocytosis. Annu. Rev. Biochem. 2010; 79:803–833. 10.1146/annurev-biochem-060208-104626
Somiya, M.; Liu, Q.; Yoshimoto, N.; Iijima, M.; Tatematsu, K.; Nakai, T.; Okajima, T.; Kuroki, K.; Ueda, K.; Kuroda, S. Cellular uptake of hepatitis B virus envelope L particles is independent of sodium taurocholate cotransporting polypeptide, but dependent on heparan sulfate proteoglycan. Virology .2016; 497:23–32. 10.1016/j.virol.2016.06.024
Barth, H., Schafer, C., Adah, M.I. et al.Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J. Biol. Chem. 2003; 278:41003–41012. 10.1074/jbc.M302267200
Volz, E.; Hill, V.; McCrone, J.T.; Price, A.; Jorgensen, D.; O’Toole, Á.; Southgate, J.; Johnson, R.; Jackson, B.; Nascimento, F.F.; et al. Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity. Cell. 2021; 184:64–75. 10.1016/j.cell.2020.11.020
Dogra, P., Martin, E.B., Williams, A. et al. Novelheparan sulfate-binding peptides for blocking herpesvirus entry. PLoS ONE.2015; 10;e0126239. 10.1371/journal.pone.0126239
Jaishankar, D., Yakoub, A.M., Bogdanov, A., Valyi-Nagy, T. and Shukla, D. Characterization of a proteolytically stable D-peptide that suppressesherpes simplex virus 1 infection: implications for the development of entry-based antiviral therapy. J. Virol.2015; 89:1932–1938. 10.1128/JVI.02979-14
Fehr, A. R., and Perlman, S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol. Biol. 2015; 1282:1–23. 10.1007/978-1-4939-2438-7_1
Su, S.,Wong, G., Shi,W., Liu, J., Lai, A. C. K., Zhou, J., et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016; 24:490–502. 10.1016/j.tim.2016.03.003
Gomes, P. B., and Dietrich, C. P. Distribution of heparin and other sulfated glycosaminoglycans in vertebrates. Comp. Biochem. Physiol. B.1982; 73:857–863. 10.1016/0305-0491(82)90329-7
Mycroft-West, C., Su, D., Elli, S., Li, Y., Guimond, S., Miller, G., et al. The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding. BioRxiv. 2020; 971093. 10.1101/2020.02.29.971093
Seffer MT, Cottam D, Forni LG, Kielstein JT. Heparin 2.0: A New Approach to the Infection Crisis. Blood Purif. 2021;50(1):28-34. 10.1159/000508647
Tang N, Bai H, Chen X, Gong J, Li D, and Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost.2020; 18:1094–1099. 10.1111/jth.14817
Tavassoly O, Safavi F, Tavassoly I. Heparin-binding Peptides as Novel Therapies to Stop SARS-CoV-2 Cellular Entry and Infection. MolPharmacol. 2020; 98(5):612-619. 10.1124/molpharm.120.000098
Herold BC, Gerber SI, Polonsky T, Belval BJ, Shaklee PN, Holme K. Identification of structural features of heparin required for inhibition of herpes simplex virus type 1 binding.Virology. 1995; 206(2):1108–16. 10.1006/viro.1995.1034
Daviet, F., Guervilly, C., Baldesi, O., Bernard-Guervilly, F., Pilarczyk, E., Genin, A., et al. Heparin induced thrombocytopenia in severe COVID-19 patients. Circulation 2020; 49015. 10.1161/CIRCULATIONAHA.120.049015
Lozano, R., and Franco, M. E. Incidence of heparin-induced thrombocytopenia in patients with 2019 coronavirus disease. Med. Clin. 2020:23.
Duranteau, J., Taccone, F. S., Verhamme, P., Ageno, W., and Force, E. V. G. T. European guidelines on perioperative venous thromboembolism prophylaxis: intensive care. Eur. J. Anaesthesiol. 2018; 35:142–146.10.1097/EJA.0000000000000707
Shi, C., Wang, C., Wang, H., Yang, C., Cai, F., Zeng, F., et al. The potential of low molecular weight heparin to mitigate cytokine storm in severe COVID-19 patients: a retrospective cohort study. Clin. Transl. Sci. 2020; 12880.10.1111/cts.12880
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