Research Progress on Antiviral Activity of Heparin

Yi      Wang; Yanqing      Zhang; Ping      Wang; Tianyuan      Jing; Yanan      Hu; Xiushan      Chen
Abstract

Heparin, as a glycosaminoglycan, is known for its anticoagulant and antithrombotic properties for several decades. Heparin is a life-saving drug and is widely used for anticoagulation in medical practice. In recent years, there have been extensive studies that heparin plays an important role in non-anticoagulant diseases, such as anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, anti-metastatic effects, and so on. Clinical observation and in vitro experiments indicate that heparin displays a potential multitarget effect. In this brief review, we will summarize heparin and its derivative's recently studied progress for the treatment of various viral infections. The aim is to maximize the benefits of drugs through medically targeted development, to meet the unmet clinical needs of serious viral diseases.
Keywords: Heparin, heparan sulfate, antiviral, heparin mimic, mechanism, virus, glycosaminoglycan.
[1]
Saikrushna, J.; Ram, S. Isolation, synthesis, and medicinal applications of heparin. Chem. Biol. Lett.,  2021, 8(2), 59-66.

[2]
Page, C. Heparin and related drugs: beyond anticoagulant activity. ISRN Pharmacol.,  2013, 2013, 910743.
 [http://dx.doi.org/10.1155/2013/910743] [PMID: 23984092]

[3]
Lima, M.; Rudd, T.; Yates, E. New applications of heparin and other glycosaminoglycans. Molecules,  2017, 22(5), 749-759.
 [http://dx.doi.org/10.3390/molecules22050749] [PMID: 28481236]

[4]
Zhang, F.; Yang, B.; Ly, M.; Solakyildirim, K.; Xiao, Z.; Wang, Z.; Beaudet, J.M.; Torelli, A.Y.; Dordick, J.S.; Linhardt, R.J. Structural characterization of heparins from different commercial sources. Anal. Bioanal. Chem.,  2011, 401(9), 2793-2803.
 [http://dx.doi.org/10.1007/s00216-011-5367-7] [PMID: 21931955]

[5]
Kamhi, E.; Joo, E.J.; Dordick, J.S.; Linhardt, R.J. Glycosaminoglycans in infectious disease. Biol. Rev. Camb. Philos. Soc.,  2013, 88(4), 928-943.
 [http://dx.doi.org/10.1111/brv.12034] [PMID: 23551941]

[6]
Mohamed, S.; Coombe, D. Heparin Mimetics: Their therapeutic potential. Pharmaceuticals (Basel),  2017, 10(4), 78-110.
 [http://dx.doi.org/10.3390/ph10040078] [PMID: 28974047]

[7]
Perlin, A.S.; Mackie, D.M.; Dietrich, C.P. Evidence for a (1→4)-linked 4-O-(α-L-idopyranosyluronic acid 2-sulfate)-(2-deoxy-2-sulfoamino-D-glucopyranosyl 6-sulfate) sequence in heparin. Carbohydr. Res,  1971, 18(2), 185-194.
 [http://dx.doi.org/10.1016/S0008-6215(00)80341-9] [PMID: 5151386]

[8]
Vilanova, E.; Vairo, B.C.; Oliveira, S.N.M.C.G.; Glauser, B.F.; Capillé, N.V.; Santos, G.R.C.; Tovar, A.M.F.; Pereira, M.S.; Mourão, P.A.S. Heparins sourced from bovine and porcine mucosa gain exclusive monographs in the brazilian pharmacopeia. Front. Med. (Lausanne),  2019, 6, 16.
 [http://dx.doi.org/10.3389/fmed.2019.00016] [PMID: 30805341]

[9]
Zhang, Z. The structural characterization of low molecular weight heparin. Chin. J. New Drugs,  2014, 23(8), 901-905+939.

[10]
Hao, C.; Sun, M.; Wang, H.; Zhang, L.; Wang, W. Low molecular weight heparins and their clinical applications. Prog. Mol. Biol. Transl. Sci.,  2019, 163, 21-39.
 [http://dx.doi.org/10.1016/bs.pmbts.2019.02.003] [PMID: 31030749]

[11]
Fu, L.; Li, G.; Yang, B.; Onishi, A.; Li, L.; Sun, P.; Zhang, F.; Linhardt, R.J. Structural characterization of pharmaceutical heparins prepared from different animal tissues. J. Pharm. Sci.,  2013, 102(5), 1447-1457.
 [http://dx.doi.org/10.1002/jps.23501] [PMID: 23526651]

[12]
Wardrop, D.; Keeling, D. The story of the discovery of heparin and warfarin. Br. J. Haematol,  2008, 141(6), 757-763.
 [http://dx.doi.org/10.1111/j.1365-2141.2008.07119.x] [PMID: 18355382]

[13]
Linhardt, R.J. Claude, S. Hudson award address in carbohydrate chemistry. Heparin: Structure and activity. J. Med. Chem.,  2003, 46(13), 2551-2564.
 [http://dx.doi.org/10.1021/jm030176m] [PMID: 12801218]

[14]
Oduah, E.; Linhardt, R.; Sharfstein, S. Heparin: Past, present, and future. Pharmaceuticals (Basel),  2016, 9(3), 38-49.
 [http://dx.doi.org/10.3390/ph9030038] [PMID: 27384570]

[15]
Spillmann, D. Heparan sulfate: Anchor for viral intruders? Biochimie,  2001, 83(8), 811-817.
 [http://dx.doi.org/10.1016/S0300-9084(01)01290-1] [PMID: 11530214]

[16]
Liu, J.; Thorp, S.C. Cell surface heparan sulfate and its roles in assisting viral infections. Med. Res. Rev.,  2002, 22(1), 1-25.
 [http://dx.doi.org/10.1002/med.1026] [PMID: 11746174]

[17]
Hendricks, G.L.; Velazquez, L.; Pham, S.; Qaisar, N.; Delaney, J.C.; Viswanathan, K.; Albers, L.; Comolli, J.C.; Shriver, Z.; Knipe, D.M.; Kurt-Jones, E.A.; Fygenson, D.K.; Trevejo, J.M.; Wang, J.P.; Finberg, R.W. Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses. Antiviral Res.,  2015, 116, 34-44.
 [http://dx.doi.org/10.1016/j.antiviral.2015.01.008] [PMID: 25637710]

[18]
Lee, E.; Pavy, M.; Young, N.; Freeman, C.; Lobigs, M. Antiviral effect of the heparan sulfate mimetic, PI-88, against dengue and encephalitic flaviviruses. Antiviral Res.,  2006, 69(1), 31-38.
 [http://dx.doi.org/10.1016/j.antiviral.2005.08.006] [PMID: 16309754]

[19]
Vervaeke, P.; Alen, M.; Noppen, S.; Schols, D.; Oreste, P.; Liekens, S. Sulfated Escherichia coli K5 polysaccharide derivatives inhibit dengue virus infection of human microvascular endothelial cells by interacting with the viral envelope protein E domain III. PLoS One,  2013, 8(8), e74035-e74047.
 [http://dx.doi.org/10.1371/journal.pone.0074035] [PMID: 24015314]

[20]
Kuhn, R.J.; Zhang, W.; Rossmann, M.G.; Pletnev, S.V.; Corver, J.; Lenches, E.; Jones, C.T.; Mukhopadhyay, S.; Chipman, P.R.; Strauss, E.G.; Baker, T.S.; Strauss, J.H. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell,  2002, 108(5), 717-725.
 [http://dx.doi.org/10.1016/S0092-8674(02)00660-8] [PMID: 11893341]

[21]
Bhatt, S.; Gething, P.W.; Brady, O.J.; Messina, J.P.; Farlow, A.W.; Moyes, C.L.; Drake, J.M.; Brownstein, J.S.; Hoen, A.G.; Sankoh, O.; Myers, M.F.; George, D.B.; Jaenisch, T.; Wint, G.R.W.; Simmons, C.P.; Scott, T.W.; Farrar, J.J.; Hay, S.I. The global distribution and burden of dengue. Nature,  2013, 496(7446), 504-507.
 [http://dx.doi.org/10.1038/nature12060] [PMID: 23563266]

[22]
Chen, Y.; Maguire, T.; Hileman, R.E.; Fromm, J.R.; Esko, J.D.; Linhardt, R.J.; Marks, R.M. Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat. Med.,  1997, 3(8), 866-871.
 [http://dx.doi.org/10.1038/nm0897-866] [PMID: 9256277]

[23]
Marks, R.M.; Lu, H.; Sundaresan, R.; Toida, T.; Suzuki, A.; Imanari, T.; Hernáiz, M.J.; Linhardt, R.J. Probing the interaction of dengue virus envelope protein with heparin: assessment of glycosaminoglycan-derived inhibitors. J. Med. Chem.,  2001, 44(13), 2178-2187.
 [http://dx.doi.org/10.1021/jm000412i] [PMID: 11405655]

[24]
Lin, Y.L.; Lei, H.Y.; Lin, Y.S.; Yeh, T.M.; Chen, S.H.; Liu, H.S. Heparin inhibits dengue-2 virus infection of five human liver cell lines. Antiviral Res.,  2002, 56(1), 93-96.
 [http://dx.doi.org/10.1016/S0166-3542(02)00095-5] [PMID: 12323403]

[25]
Talarico, L.; Pujol, C.; Zibetti, R.; Faría, P.; Noseda, M.; Duarte, M.; Damonte, E. The antiviral activity of sulfated polysaccharides against dengue virus is dependent on virus serotype and host cell. Antiviral Res.,  2005, 66(2-3), 103-110.
 [http://dx.doi.org/10.1016/j.antiviral.2005.02.001] [PMID: 15911027]

[26]
Dalrymple, N.; Mackow, E.R. Productive dengue virus infection of human endothelial cells is directed by heparan sulfate-containing proteoglycan receptors. J. Virol.,  2011, 85(18), 9478-9485.
 [http://dx.doi.org/10.1128/JVI.05008-11] [PMID: 21734047]

[27]
Modhiran, N.; Gandhi, N.S.; Wimmer, N.; Cheung, S.; Stacey, K.; Young, P.R.; Ferro, V.; Watterson, D. Dual targeting of dengue virus virions and NS1 protein with the heparan sulfate mimic PG545. Antiviral Res.,  2019, 168, 121-127.
 [http://dx.doi.org/10.1016/j.antiviral.2019.05.004] [PMID: 31085206]

[28]
de Almeida, M. M. C. S. The crab heparin-like compound exhibits a strong inhibitory effect on infections by dengue virus-2. Anti-Infective Agents,  2021, 19(1), 12-18.
 [http://dx.doi.org/10.2174/2211352518999200429105342]

[29]
Dick, G.W.A.; Kitchen, S.F.; Haddow, A.J. Zika Virus (I). Isolations and serological specificity. Trans. R. Soc. Trop. Med. Hyg.,  1952, 46(5), 509-520.
 [http://dx.doi.org/10.1016/0035-9203(52)90042-4] [PMID: 12995440]

[30]
Dick, G.W.A. Paper: Epidemiological notes on some viruses isolated in Uganda (Yellow fever, Rift Valley fever, Bwamba fever, West Nile, Mengo, Semliki forest, Bunyamwera, Ntaya, Uganda S and Zika viruses). Trans. R. Soc. Trop. Med. Hyg.,  1953, 47(1), 13-48.
 [http://dx.doi.org/10.1016/0035-9203(53)90021-2] [PMID: 13077697]

[31]
Sirohi, D.; Chen, Z.; Sun, L.; Klose, T.; Pierson, T.C.; Rossmann, M.G.; Kuhn, R.J. The 3.8 Å resolution cryo-EM structure of Zika virus. Science,  2016, 352(6284), 467-470.
 [http://dx.doi.org/10.1126/science.aaf5316] [PMID: 27033547]

[32]
D’Ortenzio, E.; Matheron, S.; de Lamballerie, X.; Hubert, B.; Piorkowski, G.; Maquart, M.; Descamps, D.; Damond, F.; Yazdanpanah, Y.; Leparc-Goffart, I. Evidence of sexual transmission of zika virus. N. Engl. J. Med.,  2016, 374(22), 2195-2198.
 [http://dx.doi.org/10.1056/NEJMc1604449] [PMID: 27074370]

[33]
Gao, H.; Lin, Y.; He, J.; Zhou, S.; Liang, M.; Huang, C.; Li, X.; Liu, C.; Zhang, P. Role of heparan sulfate in the Zika virus entry, replication, and cell death. Virology,  2019, 529, 91-100.
 [http://dx.doi.org/10.1016/j.virol.2019.01.019] [PMID: 30684694]

[34]
Maslow, J.N. Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus. Hum. Vaccin. Immunother.,  2017, 13(12), 2918-2930.
 [http://dx.doi.org/10.1080/21645515.2017.1358325] [PMID: 28846484]

[35]
Pierson, T.C.; Diamond, M.S. The emergence of Zika virus and its new clinical syndromes. Nature,  2018, 560(7720), 573-581.
 [http://dx.doi.org/10.1038/s41586-018-0446-y] [PMID: 30158602]

[36]
Kim, S.Y.; Zhao, J.; Liu, X.; Fraser, K.; Lin, L.; Zhang, X.; Zhang, F.; Dordick, J.S.; Linhardt, R.J. Interaction of Zika Virus envelope protein with glycosaminoglycans. Biochemistry,  2017, 56(8), 1151-1162.
 [http://dx.doi.org/10.1021/acs.biochem.6b01056] [PMID: 28151637]

[37]
Tan, C.W.; Sam, I.C.; Chong, W.L.; Lee, V.S.; Chan, Y.F. Polysulfonate suramin inhibits Zika virus infection. Antiviral Res.,  2017, 143, 186-194.
 [http://dx.doi.org/10.1016/j.antiviral.2017.04.017] [PMID: 28457855]

[38]
Ghezzi, S.; Cooper, L.; Rubio, A.; Pagani, I.; Capobianchi, M.R.; Ippolito, G.; Pelletier, J.; Meneghetti, M.C.Z.; Lima, M.A.; Skidmore, M.A.; Broccoli, V.; Yates, E.A.; Vicenzi, E. Heparin prevents Zika virus induced-cytopathic effects in human neural progenitor cells. Antiviral Res.,  2017, 140, 13-17.
 [http://dx.doi.org/10.1016/j.antiviral.2016.12.023] [PMID: 28063994]

[39]
Kim, S.Y.; Koetzner, C.A.; Payne, A.F.; Nierode, G.J.; Yu, Y.; Wang, R.; Barr, E.; Dordick, J.S.; Kramer, L.D.; Zhang, F.; Linhardt, R.J. Glycosaminoglycan compositional analysis of relevant tissues in zika virus pathogenesis and in vitro evaluation of heparin as an antiviral against zika virus infection. Biochemistry,  2019, 58(8), 1155-1166.
 [http://dx.doi.org/10.1021/acs.biochem.8b01267] [PMID: 30698412]

[40]
Pagani, I.; Ottoboni, L.; Podini, P.; Ghezzi, S.; Brambilla, E.; Bezukladova, S.; Corti, D.; Bianchi, M.E.; Capobianchi, M.R.; Yates, E.A.; Martino, G.; Vicenzi, E. Heparin protects human neural progenitor cells from Zika Virus-induced cell death and preserves their differentiation into mature neural-glia cells. bioRxiv,  2021, 2021, 442746.
 [http://dx.doi.org/10.1101/2021.05.05.442746]

[41]
Kleymann, G. Agents and strategies in development for improved management of herpes simplex virus infection and disease. Expert Opin. Investig. Drugs,  2005, 14(2), 135-161.
 [http://dx.doi.org/10.1517/13543784.14.2.135] [PMID: 15757392]

[42]
Jiang, Y.C.; Feng, H.; Lin, Y.C.; Guo, X.R. New strategies against drug resistance to herpes simplex virus. Int. J. Oral Sci.,  2016, 8(1), 1-6.
 [http://dx.doi.org/10.1038/ijos.2016.3] [PMID: 27025259]

[43]
Looker, K.J.; Welton, N.J.; Sabin, K.M.; Dalal, S.; Vickerman, P.; Turner, K.M.E.; Boily, M.C.; Gottlieb, S.L. Global and regional estimates of the contribution of herpes simplex virus type 2 infection to HIV incidence: a population attributable fraction analysis using published epidemiological data. Lancet Infect. Dis.,  2020, 20(2), 240-249.
 [http://dx.doi.org/10.1016/S1473-3099(19)30470-0] [PMID: 31753763]

[44]
Chou, S. Cytomegalovirus UL97 mutations in the era of ganciclovir and maribavir. Rev. Med. Virol.,  2008, 18(4), 233-246.
 [http://dx.doi.org/10.1002/rmv.574] [PMID: 18383425]

[45]
Pouyan, P.; Nie, C.; Bhatia, S.; Wedepohl, S.; Achazi, K.; Osterrieder, N.; Haag, R. Inhibition of herpes simplex virus type 1 attachment and infection by sulfated polyglycerols with different architectures. Biomacromolecules,  2021, 22(4), 1545-1554.
 [http://dx.doi.org/10.1021/acs.biomac.0c01789] [PMID: 33706509]

[46]
Lischka, P.; Zimmermann, H. Antiviral strategies to combat cytomegalovirus infections in transplant recipients. Curr. Opin. Pharmacol.,  2008, 8(5), 541-548.
 [http://dx.doi.org/10.1016/j.coph.2008.07.002] [PMID: 18662804]

[47]
Andrei, G.; De Clercq, E.; Snoeck, R. Drug targets in cytomegalovirus infection. Infect. Disord. Drug Targets,  2009, 9(2), 201-222.
 [http://dx.doi.org/10.2174/187152609787847758] [PMID: 19275707]

[48]
WuDunn, D.; Spear, P.G. Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J. Virol.,  1989, 63(1), 52-58.
 [http://dx.doi.org/10.1128/jvi.63.1.52-58.1989] [PMID: 2535752]

[49]
Trybala, E.; Liljeqvist, J.A.; Svennerholm, B.; Bergström, T. Herpes simplex virus types 1 and 2 differ in their interaction with heparan sulfate. J. Virol.,  2000, 74(19), 9106-9114.
 [http://dx.doi.org/10.1128/JVI.74.19.9106-9114.2000] [PMID: 10982357]

[50]
Herold, B.C.; Gerber, S.I.; Polonsky, T.; Belval, B.J.; Shaklee, P.N.; Holme, K. Identification of structural features of heparin required for inhibition of herpes simplex virus type 1 binding. Virology,  1995, 206(2), 1108-1116.
 [http://dx.doi.org/10.1006/viro.1995.1034] [PMID: 7856085]

[51]
Copeland, R.; Balasubramaniam, A.; Tiwari, V.; Zhang, F.; Bridges, A.; Linhardt, R.J.; Shukla, D.; Liu, J. Using a 3-O-sulfated heparin octasaccharide to inhibit the entry of herpes simplex virus type 1. Biochemistry,  2008, 47(21), 5774-5783.
 [http://dx.doi.org/10.1021/bi800205t] [PMID: 18457417]

[52]
Shukla, D.; Liu, J.; Blaiklock, P.; Shworak, N.W.; Bai, X.; Esko, J.D.; Cohen, G.H.; Eisenberg, R.J.; Rosenberg, R.D.; Spear, P.G. A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell,  1999, 99(1), 13-22.
 [http://dx.doi.org/10.1016/S0092-8674(00)80058-6] [PMID: 10520990]

[53]
Hu, Y.P.; Lin, S.Y.; Huang, C.Y.; Zulueta, M.M.L.; Liu, J.Y.; Chang, W.; Hung, S.C. Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host–cell interaction. Nat. Chem.,  2011, 3(7), 557-563.
 [http://dx.doi.org/10.1038/nchem.1073] [PMID: 21697878]

[54]
Lembo, D.; Donalisio, M.; Laine, C.; Cagno, V.; Civra, A.; Bianchini, E.P.; Zeghbib, N.; Bouchemal, K. Auto-associative heparin nanoassemblies: A biomimetic platform against the heparan sulfate-dependent viruses HSV-1, HSV-2, HPV-16 and RSV. Eur. J. Pharm. Biopharm.,  2014, 88(1), 275-282.
 [http://dx.doi.org/10.1016/j.ejpb.2014.05.007] [PMID: 24835150]

[55]
Mese, K.; Bunz, O.; Volkwein, W.; Vemulapalli, S.P.B.; Zhang, W.; Schellhorn, S.; Heenemann, K.; Rueckner, A.; Sing, A.; Vahlenkamp, T.W.; Severing, A.L.; Gao, J.; Aydin, M.; Jung, D.; Bachmann, H.S.; Zänker, K.S.; Busch, U.; Baiker, A.; Griesinger, C.; Ehrhardt, A. Enhanced antiviral function of magnesium chloride-modified heparin on a broad spectrum of viruses. Int. J. Mol. Sci.,  2021, 22(18), 10075-10088.
 [http://dx.doi.org/10.3390/ijms221810075] [PMID: 34576237]

[56]
Ahmadi, V.; Nie, C.; Mohammadifar, E.; Achazi, K.; Wedepohl, S.; Kerkhoff, Y.; Block, S.; Osterrieder, K.; Haag, R. One-pot gram-scale synthesis of virucidal heparin-mimicking polymers as HSV-1 inhibitors. Chem. Commun. (Camb.),  2021, 57(90), 11948-11951.
 [http://dx.doi.org/10.1039/D1CC04703E] [PMID: 34671786]

[57]
Jana, S.; Mukherjee, S.; Ribelato, E.V.; Darido, M.L.; Faccin-Galhardi, L.C.; Ray, B.; Ray, S. The heparin-mimicking arabinogalactan sulfates from Anogeissus latifolia gum: Production, structures, and anti-herpes simplex virus activity. Int. J. Biol. Macromol.,  2021, 183, 1419-1426.
 [http://dx.doi.org/10.1016/j.ijbiomac.2021.05.107] [PMID: 34022307]

[58]
Bergeron, H.C.; Murray, J.; Nuñez Castrejon, A.M.; DuBois, R.M.; Tripp, R.A. Respiratory syncytial virus (RSV) G protein vaccines with central conserved domain mutations induce CX3C-CX3CR1 blocking antibodies. Viruses,  2021, 13(2), 352-368.
 [http://dx.doi.org/10.3390/v13020352] [PMID: 33672319]

[59]
Chatzis, O.; Darbre, S.; Pasquier, J.; Meylan, P.; Manuel, O.; Aubert, J.D.; Beck-Popovic, M.; Masouridi-Levrat, S.; Ansari, M.; Kaiser, L.; Posfay-Barbe, K.M.; Asner, S.A. Burden of severe RSV disease among immunocompromised children and adults: a 10 year retrospective study. BMC Infect. Dis.,  2018, 18(1), 111.
 [http://dx.doi.org/10.1186/s12879-018-3002-3] [PMID: 29510663]

[60]
Piedimonte, G.; Perez, M.K. Respiratory syncytial virus infection and bronchiolitis. Pediatr. Rev.,  2014, 35(12), 519-530.
 [http://dx.doi.org/10.1542/pir.35.12.519] [PMID: 25452661]

[61]
Cagno, V.; Donalisio, M.; Civra, A.; Volante, M.; Veccelli, E.; Oreste, P.; Rusnati, M.; Lembo, D. Highly sulfated K5 Escherichia coli polysaccharide derivatives inhibit respiratory syncytial virus infectivity in cell lines and human tracheal-bronchial histocultures. Antimicrob. Agents Chemother.,  2014, 58(8), 4782-4794.
 [http://dx.doi.org/10.1128/AAC.02594-14] [PMID: 24914125]

[62]
Cagno, V.; Tseligka, E.D.; Jones, S.T.; Tapparel, C. Heparan sulfate proteoglycans and viral attachment: True receptors or adaptation bias? Viruses,  2019, 11(7), 596.
 [http://dx.doi.org/10.3390/v11070596] [PMID: 31266258]

[63]
Feldman, S.A.; Hendry, R.M.; Beeler, J.A. Identification of a linear heparin binding domain for human respiratory syncytial virus attachment glycoprotein G. J. Virol.,  1999, 73(8), 6610-6617.
 [http://dx.doi.org/10.1128/JVI.73.8.6610-6617.1999] [PMID: 10400758]

[64]
Feldman, S.A.; Audet, S.; Beeler, J.A. The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate. J. Virol.,  2000, 74(14), 6442-6447.
 [http://dx.doi.org/10.1128/JVI.74.14.6442-6447.2000] [PMID: 10864656]

[65]
Donalisio, M.; Rusnati, M.; Cagno, V.; Civra, A.; Bugatti, A.; Giuliani, A.; Pirri, G.; Volante, M.; Papotti, M.; Landolfo, S.; Lembo, D. Inhibition of human respiratory syncytial virus infectivity by a dendrimeric heparan sulfate-binding peptide. Antimicrob. Agents Chemother.,  2012, 56(10), 5278-5288.
 [http://dx.doi.org/10.1128/AAC.00771-12] [PMID: 22850525]

[66]
Krusat, T.; Streckert, H.J. Heparin-dependent attachment ofrespiratory syncytial virus (RSV) to host cells. Arch. Virol.,  1997, 142(6), 1247-1254.
 [http://dx.doi.org/10.1007/s007050050156] [PMID: 9229012]

[67]
Hallak, L.K.; Spillmann, D.; Collins, P.L.; Peeples, M.E. Glycosaminoglycan sulfation requirements for respiratory syncytial virus infection. J. Virol.,  2000, 74(22), 10508-10513.
 [http://dx.doi.org/10.1128/JVI.74.22.10508-10513.2000] [PMID: 11044095]

[68]
Guo, Y.; Wang, Z.; Dong, L.; Wu, J.; Zhai, S.; Liu, D. Ability of low-molecular-weight heparin to alleviate proteinuria by inhibiting respiratory syncytial virus infection. Nephrology (Carlton),  2008, 13(7), 545-553.
 [http://dx.doi.org/10.1111/j.1440-1797.2008.01012.x] [PMID: 19161362]

[69]
Johnson, S.M.; McNally, B.A.; Ioannidis, I.; Flano, E.; Teng, M.N.; Oomens, A.G.; Walsh, E.E.; Peeples, M.E. Respiratory syncytial virus Uses CX3CR1 as a receptor on primary human airway epithelial cultures. PLoS Pathog.,  2015, 11(12), e1005318-e1005333.
 [http://dx.doi.org/10.1371/journal.ppat.1005318] [PMID: 26658574]

[70]
Chirkova, T.; Lin, S.; Oomens, A.G.P.; Gaston, K.A.; Boyoglu-Barnum, S.; Meng, J.; Stobart, C.C.; Cotton, C.U.; Hartert, T.V.; Moore, M.L.; Ziady, A.G.; Anderson, L.J. CX3CR1 is an important surface molecule for respiratory syncytial virus infection in human airway epithelial cells. J. Gen. Virol.,  2015, 96(9), 2543-2556.
 [http://dx.doi.org/10.1099/vir.0.000218] [PMID: 26297201]

[71]
Zhang, L.; Bukreyev, A.; Thompson, C.I.; Watson, B.; Peeples, M.E.; Collins, P.L.; Pickles, R.J. Infection of ciliated cells by human parainfluenza virus type 3 in an in vitro model of human airway epithelium. J. Virol.,  2005, 79(2), 1113-1124.
 [http://dx.doi.org/10.1128/JVI.79.2.1113-1124.2005] [PMID: 15613339]

[72]
William, D.; James, M.D.; Dirk, M.; Elston, M.D.; James, R.; Treat, M.D.; Misha, A.; Rosenbach, M.D.; Isaac, M.; Neuhaus, M.D. Viral Diseases. In:  Andrews' Diseases of the Skin; Elsevier, Amsterdam, 2020; 19, pp. 362-420.

[73]
Walker, S.L.; Grayson, W. Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS)-associated cutaneous diseases. In: McKee's Pathology of the Skin, 5th ed.; Elsevier, Amsterdam, 2020; pp. 976-989.e5.

[74]
Patel, M.; Yanagishita, M.; Roderiquez, G.; Bou-Habib, D.C.; Oravecz, T.; Hascall, V.C.; Norcross, M.A. Cell-surface heparan sulfate proteoglycan mediates HIV-1 infection of T-cell lines. AIDS Res. Hum. Retroviruses,  1993, 9(2), 167-174.
 [http://dx.doi.org/10.1089/aid.1993.9.167] [PMID: 8096145]

[75]
Mbemba, E.; Czyrski, J.A.; Gattegno, L. The interaction of a glycosaminoglycan heparin, with HIV-1 major envelope glycoprotein. Biochim. Biophys. Acta Mol. Basis Dis.,  1992, 1180(2), 123-129.
 [http://dx.doi.org/10.1016/0925-4439(92)90060-Z] [PMID: 1281430]

[76]
Howell, A.L.; Taylor, T.H.; Miller, J.D.; Groveman, D.S.; Eccles, E.H.; Zacharski, L.R. Inhibition of HIV-1 infectivity by low molecular weight heparin. Int. J. Clin. Lab. Res.,  1996, 26(2), 124-131.
 [http://dx.doi.org/10.1007/BF02592355] [PMID: 8856366]

[77]
Harrop, H.A.; Rider, C.C. Heparin and its derivatives bind to HIV-1 recombinant envelope glycoproteins, rather than to recombinant HIV-1 receptor, CD4. Glycobiology,  1998, 8(2), 131-137.
 [http://dx.doi.org/10.1093/glycob/8.2.131] [PMID: 9451022]

[78]
Vivès, R.R.; Imberty, A.; Sattentau, Q.J.; Lortat-Jacob, H. Heparan sulfate targets the HIV-1 envelope glycoprotein gp120 coreceptor binding site. J. Biol. Chem.,  2005, 280(22), 21353-21357.
 [http://dx.doi.org/10.1074/jbc.M500911200] [PMID: 15797855]

[79]
Mohan, P.; Schols, D.; Baba, M.; De Clercq, E. Sulfonic acid polymers as a new class of human immunodeficiency virus inhibitors. Antiviral Res.,  1992, 18(2), 139-150.
 [http://dx.doi.org/10.1016/0166-3542(92)90034-3] [PMID: 1384428]

[80]
Bugatti, A.; Urbinati, C.; Ravelli, C.; De Clercq, E.; Liekens, S.; Rusnati, M. Heparin-mimicking sulfonic acid polymers as multitarget inhibitors of human immunodeficiency virus type 1 Tat and gp120 proteins. Antimicrob. Agents Chemother.,  2007, 51(7), 2337-2345.
 [http://dx.doi.org/10.1128/AAC.01362-06] [PMID: 17452490]

[81]
Nassar, R.A.; Browne, E.P.; Chen, J.; Klibanov, A.M. Removing human immunodeficiency virus (HIV) from human blood using immobilized heparin. Biotechnol. Lett.,  2012, 34(5), 853-856.
 [http://dx.doi.org/10.1007/s10529-011-0840-0] [PMID: 22207147]

[82]
Pasquato, A.; Dettin, M.; Basak, A.; Gambaretto, R.; Tonin, L.; Seidah, N.G.; Di Bello, C. Heparin enhances the furin cleavage of HIV-1 gp160 peptides. FEBS Lett.,  2007, 581(30), 5807-5813.
 [http://dx.doi.org/10.1016/j.febslet.2007.11.050] [PMID: 18037384]

[83]
Crublet, E.; Andrieu, J.P.; Vivès, R.R.; Lortat-Jacob, H. The HIV-1 envelope glycoprotein gp120 features four heparan sulfate binding domains, including the co-receptor binding site. J. Biol. Chem.,  2008, 283(22), 15193-15200.
 [http://dx.doi.org/10.1074/jbc.M800066200] [PMID: 18378683]

[84]
Plotnik, D.; Guo, W.; Cleveland, B.; von Haller, P.; Eng, J.K.; Guttman, M.; Lee, K.K.; Arthos, J.; Hu, S.L. Extracellular matrix proteins mediate HIV-1 gp120 interactions with α 4 β 7. J. Virol.,  2017, 91(21), e01005-17.
 [http://dx.doi.org/10.1128/JVI.01005-17] [PMID: 28814519]

[85]
Bugatti, A.; Paiardi, G.; Urbinati, C.; Chiodelli, P.; Orro, A.; Uggeri, M.; Milanesi, L.; Caruso, A.; Caccuri, F.; D’Ursi, P.; Rusnati, M. Heparin and heparan sulfate proteoglycans promote HIV-1 p17 matrix protein oligomerization: computational, biochemical and biological implications. Sci. Rep.,  2019, 9(1), 15768-15779.
 [http://dx.doi.org/10.1038/s41598-019-52201-w] [PMID: 31673058]

[86]
Meselson, M. Droplets and aerosols in the transmission of SARS-CoV-2. N. Engl. J. Med.,  2020, 382(21), 2063.
 [http://dx.doi.org/10.1056/NEJMc2009324] [PMID: 32294374]

[87]
Wadman, M.; Couzin-Frankel, J.; Kaiser, J.; Matacic, C. A rampage through the body. Science,  2020, 368(6489), 356-360.
 [http://dx.doi.org/10.1126/science.368.6489.356] [PMID: 32327580]

[88]
Conzelmann, C.; Müller, J.A.; Perkhofer, L.; Sparrer, K.M.J.; Zelikin, A.N.; Münch, J.; Kleger, A. Inhaled and systemic heparin as a repurposed direct antiviral drug for prevention and treatment of COVID-19. Clin. Med. (Lond.),  2020, 20(6), e218-e221.
 [http://dx.doi.org/10.7861/clinmed.2020-0351] [PMID: 32863274]

[89]
Tandon, R.; Sharp, J.S.; Zhang, F.; Pomin, V.H.; Ashpole, N.M.; Mitra, D.; McCandless, M.G.; Jin, W.; Liu, H.; Sharma, P.; Linhardt, R.J. Effective inhibition of SARS-CoV-2 entry by heparin and enoxaparin derivatives. J. Virol.,  2021, 95(3), e01987-20.
 [http://dx.doi.org/10.1128/JVI.01987-20] [PMID: 33173010]

[90]
Clausen, T.M.; Sandoval, D.R.; Spliid, C.B.; Pihl, J.; Perrett, H.R.; Painter, C.D.; Narayanan, A.; Majowicz, S.A.; Kwong, E.M.; McVicar, R.N.; Thacker, B.E.; Glass, C.A.; Yang, Z.; Torres, J.L.; Golden, G.J.; Bartels, P.L.; Porell, R.N.; Garretson, A.F.; Laubach, L.; Feldman, J.; Yin, X.; Pu, Y.; Hauser, B.M.; Caradonna, T.M.; Kellman, B.P.; Martino, C.; Gordts, P.L.S.M.; Chanda, S.K.; Schmidt, A.G.; Godula, K.; Leibel, S.L.; Jose, J.; Corbett, K.D.; Ward, A.B.; Carlin, A.F.; Esko, J.D. 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]

[91]
Oppenheimer, S. Covid-19 pandemic, glycobiology, glycan shields, vaccine strategies, heparin sulfate: A mini review. Am. J. Appl. Sci. Res.,  2020, 6(2), 46-48.
 [http://dx.doi.org/10.11648/j.ajasr.20200602.14]

[92]
Vicenzi, E.; Canducci, F.; Pinna, D.; Mancini, N.; Carletti, S.; Lazzarin, A.; Bordignon, C.; Poli, G.; Clementi, M. Coronaviridae and SARS-associated coronavirus strain HSR1. Emerg. Infect. Dis.,  2004, 10(3), 413-418.
 [http://dx.doi.org/10.3201/eid1003.030683] [PMID: 15109406]

[93]
Mycroft-West, C.; Su, D.; Elli, S.; Li, Y.; Guimond, S.; Miller, G.; Turnbull, J.; Yates, E.; Guerrini, M.; Fernig, D.; Lima, M.; Skidmore, M. The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1Receptor Binding Domain undergoes conformational change upon heparin binding. bioRxiv,  2020, 2020, 971093v2.

[94]
Mycroft-West, C.J.; Su, D.; Pagani, I.; Rudd, T.R.; Elli, S.; Guimond, S.E.; Miller, G.; Meneghetti, M.C.Z.; Nader, H.B.; Li, Y.; Nunes, Q.M.; Procter, P.; Mancini, N.; Clementi, M.; Bisio, A.; Forsyth, N.R.; Turnbull, J.E.; Guerrini, M.; Fernig, D.G.; Vicenzi, E.; Yates, E.A.; Lima, M.A.; Skidmore, M.A. Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the surface protein (spike) S1 receptor binding domain with heparin. bioRxiv,  2020, 2020, 066761.
 [http://dx.doi.org/10.1101/2020.04.28.066761]

[95]
Kim, S.Y.; Jin, W.; Sood, A.; Montgomery, D.W.; Grant, O.C.; Fuster, M.M.; Fu, L.; Dordick, J.S.; Woods, R.J.; Zhang, F.; Linhardt, R.J. Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions. Antiviral Res.,  2020, 181, 104873.
 [http://dx.doi.org/10.1016/j.antiviral.2020.104873] [PMID: 32653452]

[96]
Liu, L.; Chopra, P.; Li, X.R.; Wolfert, M.A.; Tompkins, S.M.; Boons, G-J. SARS-CoV-2 spike protein binds heparan sulfate in a length- and sequence-dependent manner. bioRxiv,  2020, 2020, 087288.

[97]
Paiardi, G.; Richter, S.; Oreste, P.; Urbinati, C.; Rusnati, M.; Wade, R.C. Three-fold mechanism of inhibition of SARS-CoV-2 infection by the interaction of the spike glycoprotein with heparin. arXiv,  2021, 2103, 07722.

[98]
Gupta, Y.; Maciorowski, D.; Zak, S.E.; Kulkarni, C.V.; Herbert, A.S.; Durvasula, R.; Fareed, J.; Dye, J.M.; Kempaiah, P. Heparin: A simplistic repurposing to prevent SARS-CoV-2 transmission in light of its in-vitro nanomolar efficacy. Int. J. Biol. Macromol.,  2021, 183, 203-212.
 [http://dx.doi.org/10.1016/j.ijbiomac.2021.04.148] [PMID: 33915212]

[99]
Li, J.; Zhang, Y.; Pang, H.; Li, S.J. Heparin interacts with the main protease of SARS-CoV-2 and inhibits its activity. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2022, 267(Pt 2), 120595.
 [http://dx.doi.org/10.1016/j.saa.2021.120595] [PMID: 34815178]

[100]
Paiardi, G.; Richter, S.; Oreste, P.; Urbinati, C.; Rusnati, M.; Wade, R.C. The binding of heparin to spike glycoprotein inhibits SARS-CoV-2 infection by three mechanisms. J. Biol. Chem.,  2022, 298(2), 101507.
 [http://dx.doi.org/10.1016/j.jbc.2021.101507] [PMID: 34929169]

[101]
Partridge, L.J.; Urwin, L.; Nicklin, M.J.H.; James, D.C.; Green, L.R.; Monk, P.N. ACE2-independent interaction of SARS-CoV-2 spike protein with human epithelial cells is inhibited by unfractionated heparin. Cells,  2021, 10(6), 1419.
 [http://dx.doi.org/10.3390/cells10061419] [PMID: 34200372]

[102]
Tree, J.A.; Turnbull, J.E.; Buttigieg, K.R.; Elmore, M.J.; Coombes, N.; Hogwood, J.; Mycroft-West, C.J.; Lima, M.A.; Skidmore, M.A.; Karlsson, R.; Chen, Y.H.; Yang, Z.; Spalluto, C.M.; Staples, K.J.; Yates, E.A.; Gray, E.; Singh, D.; Wilkinson, T.; Page, C.P.; Carroll, M.W. Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations. Br. J. Pharmacol.,  2021, 178(3), 626-635.
 [http://dx.doi.org/10.1111/bph.15304] [PMID: 33125711]

[103]
Yang, Y.; Du, Y.; Kaltashov, I.A. The utility of native ms for understanding the mechanism of action of repurposed therapeutics in COVID-19: Heparin as a disruptor of the SARS-CoV-2 interaction with its host cell receptor. Anal. Chem.,  2020, 92(16), 10930-10934.
 [http://dx.doi.org/10.1021/acs.analchem.0c02449] [PMID: 32678978]

[104]
Guimond, S.E.; Mycroft-West, C.J.; Gandhi, N.S.; Tree, J.A.; Le, T.T.; Spalluto, C.M.; Humbert, M.V.; Buttigieg, K.R.; Coombes, N.; Elmore, M.J.; Nyström, K.; Said, J.; Setoh, Y.X.; Amarilla, A.A.; Modhiran, N.; Sng, J.D.J.; Chhabra, M.; Young, P.R.; Lima, M.A.; Yates, A.E; Karlsson, R; Miller, R.L; Chen, Y.-H; Bagdonaite, I.; Yang, Z.; Stewart, J.; Hammond, E.; Dredge, K.; Wilkinson, T.M.A.; Watterson, D.; Khromykh, A.A.; Suhrbier, A.; Carroll, M.W.; Trybala, E.; Bergström, T.; Ferro, V.; Skidmore, M.A.; Turnbull, J.E. Pixatimod (PG545), a clinical-stage heparan sulfate mimetic, is a potent inhibitor of the SARS1-CoV-2 virus. bioRxiv,  2021, 2021, 169334.

[105]
Guimond, S.E.; Mycroft-West, C.J.; Gandhi, N.S.; Tree, J.A.; Le, T.T.; Spalluto, C.M.; Humbert, M.V.; Buttigieg, K.R.; Coombes, N.; Elmore, M.J.; Nyström, K.; Said, J.; Setoh, Y.X.; Amarilla, A.A.; Modhiran, N.; Sng, J.D.J.; Chhabra, M.; Young, P.R.; Lima, M.A.; Yates, A.; Karlsson, R; Miller, R.L; Chen, Y.-H; Bagdonaite, I.; Yang, Z.; Stewart, J.; Hammond, E.; Dredge, K.; Wilkinson, T.M.A.; Watterson, D.; Khromykh, A.A.; Suhrbier, A.; Carroll, M.W.; Trybala, E.; Bergström, T.; Ferro, V.; Skidmore, M.A.; Turnbull, J.E.  Synthetic heparan sulfate mimetic pixatimod (PG545) potently inhibits SARS-CoV-2 by disrupting the spike-ACE2 interaction. bioRxiv,  2020, 2020, 169334.

[106]
Tavassoly, O.; Safavi, F.; Tavassoly, I. Heparin-binding peptides as novel therapies to stop SARS-CoV-2 cellular entry and infection. Mol. Pharmacol.,  2020, 98(5), 612-619.
 [http://dx.doi.org/10.1124/molpharm.120.000098] [PMID: 32913137]

[107]
Liu, J.; Li, J.; Arnold, K.; Pawlinski, R.; Key, N.S. Using heparin molecules to manage COVID-2019. Res. Pract. Thromb. Haemost.,  2020, 4(4), 518-523.
 [http://dx.doi.org/10.1002/rth2.12353] [PMID: 32542212]

[108]
van Haren, F.M.P.; Page, C.; Laffey, J.G.; Artigas, A.; Camprubi-Rimblas, M.; Nunes, Q.; Smith, R.; Shute, J.; Carroll, M.; Tree, J.; Carroll, M.; Singh, D.; Wilkinson, T.; Dixon, B. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit. Care,  2020, 24(1), 454.
 [http://dx.doi.org/10.1186/s13054-020-03148-2] [PMID: 32698853]

[109]
Doorbar, J.; Quint, W.; Banks, L.; Bravo, I.G.; Stoler, M.; Broker, T.R.; Stanley, M.A. The biology and life-cycle of human papillomaviruses. Vaccine,  2012, 30(5)(Suppl. 5), F55-F70.
 [http://dx.doi.org/10.1016/j.vaccine.2012.06.083] [PMID: 23199966]

[110]
Gonzalez, D.; Ragusa, J.; Angeletti, P.C.; Larsen, G. Preparation and characterization of functionalized heparin-loaded poly-Ɛ-caprolactone fibrous mats to prevent infection with human papillomaviruses. PLoS One,  2018, 13(7), e0199925.
 [http://dx.doi.org/10.1371/journal.pone.0199925] [PMID: 29966006]

[111]
Surviladze, Z.; Dziduszko, A.; Ozbun, M.A. Essential roles for soluble virion-associated heparan sulfonated proteoglycans and growth factors in human papillomavirus infections. PLoS Pathog.,  2012, 8(2), e1002519.
 [http://dx.doi.org/10.1371/journal.ppat.1002519] [PMID: 22346752]

[112]
Sun, J.; Yu, J.S.; Jin, S.; Zha, X.; Wu, Y.; Yu, Z. Interaction of synthetic HPV-16 capsid peptides with heparin: thermodynamic parameters and binding mechanism. J. Phys. Chem. B,  2010, 114(30), 9854-9861.
 [http://dx.doi.org/10.1021/jp1009719] [PMID: 20666526]

[113]
Joyce, J.G.; Tung, J.S.; Przysiecki, C.T.; Cook, J.C.; Lehman, E.D.; Sands, J.A.; Jansen, K.U.; Keller, P.M. The L1 major capsid protein of human papillomavirus type 11 recombinant virus-like particles interacts with heparin and cell-surface glycosaminoglycans on human keratinocytes. J. Biol. Chem.,  1999, 274(9), 5810-5822.
 [http://dx.doi.org/10.1074/jbc.274.9.5810] [PMID: 10026203]

[114]
Donalisio, M.; Rusnati, M.; Civra, A.; Bugatti, A.; Allemand, D.; Pirri, G.; Giuliani, A.; Landolfo, S.; Lembo, D. Identification of a dendrimeric heparan sulfate-binding peptide that inhibits infectivity of genital types of human papillomaviruses. Antimicrob. Agents Chemother.,  2010, 54(10), 4290-4299.
 [http://dx.doi.org/10.1128/AAC.00471-10] [PMID: 20643894]

[115]
Giroglou, T.; Florin, L.; Schäfer, F.; Streeck, R.E.; Sapp, M. Human papillomavirus infection requires cell surface heparan sulfate. J. Virol.,  2001, 75(3), 1565-1570.
 [http://dx.doi.org/10.1128/JVI.75.3.1565-1570.2001] [PMID: 11152531]

[116]
Johnson, K.M.; Kines, R.C.; Roberts, J.N.; Lowy, D.R.; Schiller, J.T.; Day, P.M. Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus. J. Virol.,  2009, 83(5), 2067-2074.
 [http://dx.doi.org/10.1128/JVI.02190-08] [PMID: 19073722]

[117]
Richards, K. F.; Bienkowska-Haba, M.; Dasgupta, J.; Chen, X. S.; Sapp, M. Multiple heparan sulfate binding site engagements are required for the infectious entry of human papillomavirus type 16. J. Virol.,  2013, 87(21), 11426-37.

[118]
Guan, J.; Bywaters, S.M.; Brendle, S.A.; Ashley, R.E.; Makhov, A.M.; Conway, J.F.; Christensen, N.D.; Hafenstein, S. Cryoelectron microscopy maps of human papillomavirus 16 reveal L2 densities and heparin binding site. Structure,  2017, 25(2), 253-263.
 [http://dx.doi.org/10.1016/j.str.2016.12.001] [PMID: 28065506]

[119]
Gao, Y.; Liu, W.; Wang, W.; Zhang, X.; Zhao, X. The inhibitory effects and mechanisms of 3,6-O-sulfated chitosan against human papillomavirus infection. Carbohydr. Polym.,  2018, 198, 329-338.
 [http://dx.doi.org/10.1016/j.carbpol.2018.06.096] [PMID: 30093007]

[120]
Leistner, C.M.; Gruen-Bernhard, S.; Glebe, D. Role of glycosaminoglycans for binding and infection of hepatitis B virus. Cell. Microbiol.,  2008, 10(1), 122-133.
 [http://dx.doi.org/10.1111/j.1462-5822.2007.01023.x] [PMID: 18086046]

[121]
Lamas Longarela, O.; Schmidt, T.T.; Schöneweis, K.; Romeo, R.; Wedemeyer, H.; Urban, S.; Schulze, A. Proteoglycans act as cellular hepatitis delta virus attachment receptors. PLoS One,  2013, 8(3), e58340.
 [http://dx.doi.org/10.1371/journal.pone.0058340] [PMID: 23505490]

[122]
Ying, C.; Van Pelt, J.F.; Van Lommel, A.; Van Ranst, M.; Leyssen, P.; De Clercq, E.; Neyts, J. Sulphated and sulphonated polymers inhibit the initial interaction of hepatitis B virus with hepatocytes. Antivir. Chem. Chemother.,  2002, 13(3), 157-164.
 [http://dx.doi.org/10.1177/095632020201300302] [PMID: 12448688]

[123]
Zahn, A.; Allain, J.P. Hepatitis C virus and hepatitis B virus bind to heparin: purification of largely IgG-free virions from infected plasma by heparin chromatography. J. Gen. Virol.,  2005, 86(3), 677-685.
 [http://dx.doi.org/10.1099/vir.0.80614-0] [PMID: 15722528]

[124]
Schulze, A.; Gripon, P.; Urban, S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology,  2007, 46(6), 1759-1768.
 [http://dx.doi.org/10.1002/hep.21896] [PMID: 18046710]

[125]
Choijilsuren, G.; Jhou, R.S.; Chou, S.F.; Chang, C.J.; Yang, H.I.; Chen, Y.Y.; Chuang, W.L.; Yu, M.L.; Shih, C. Heparin at physiological concentration can enhance PEG-free in vitro infection with human hepatitis B virus. Sci. Rep.,  2017, 7(1), 14461.
 [http://dx.doi.org/10.1038/s41598-017-14573-9] [PMID: 29089529]

[126]
Liu, Q.; Somiya, M.; Iijima, M.; Tatematsu, K.; Kuroda, S. A hepatitis B virus-derived human hepatic cell-specific heparin-binding peptide: identification and application to a drug delivery system. Biomater. Sci.,  2019, 7(1), 322-335.
 [http://dx.doi.org/10.1039/C8BM01134F] [PMID: 30474653]

[127]
Vieyres, G.; Thomas, X.; Descamps, V.; Duverlie, G.; Patel, A.H.; Dubuisson, J. Characterization of the envelope glycoproteins associated with infectious hepatitis C virus. J. Virol.,  2010, 84(19), 10159-10168.
 [http://dx.doi.org/10.1128/JVI.01180-10] [PMID: 20668082]

[128]
Morikawa, K.; Zhao, Z.; Date, T.; Miyamoto, M.; Murayama, A.; Akazawa, D.; Tanabe, J.; Sone, S.; Wakita, T. The roles of CD81 and glycosaminoglycans in the adsorption and uptake of infectious HCV particles. J. Med. Virol.,  2007, 79(6), 714-723.
 [http://dx.doi.org/10.1002/jmv.20842] [PMID: 17457918]

[129]
LeBlanc, E.V.; Kim, Y.; Capicciotti, C.J.; Colpitts, C.C.; Hepatitis, C. Hepatitis C virus glycan-dependent interactions and the potential for novel preventative strategies. Pathogens,  2021, 10(6), 685.
 [http://dx.doi.org/10.3390/pathogens10060685] [PMID: 34205894]

[130]
Germi, R.; Crance, J.M.; Garin, D.; Guimet, J.; Lortat-Jacob, H.; Ruigrok, R.W.H.; Zarski, J.P.; Drouet, E. Cellular glycosaminoglycans and low density lipoprotein receptor are involved in hepatitis C virus adsorption. J. Med. Virol.,  2002, 68(2), 206-215.
 [http://dx.doi.org/10.1002/jmv.10196] [PMID: 12210409]

[131]
Barth, H.; Schäfer, C.; Adah, M.I.; Zhang, F.; Linhardt, R.J.; Toyoda, H.; Kinoshita-Toyoda, A.; Toida, T.; van Kuppevelt, T.H.; Depla, E.; von Weizsäcker, F.; Blum, H.E.; Baumert, T.F. Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J. Biol. Chem.,  2003, 278(42), 41003-41012.
 [http://dx.doi.org/10.1074/jbc.M302267200] [PMID: 12867431]

[132]
Olenina, L.V.; Kuzmina, T.I.; Sobolev, B.N.; Kuraeva, T.E.; Kolesanova, E.F.; Archakov, A.I. Identification of glycosaminoglycan-binding sites within hepatitis C virus envelope glycoprotein E2*. J. Viral Hepat.,  2005, 12(6), 584-593.
 [http://dx.doi.org/10.1111/j.1365-2893.2005.00647.x] [PMID: 16255759]

[133]
Barth, H.; Schnober, E.K.; Zhang, F.; Linhardt, R.J.; Depla, E.; Boson, B.; Cosset, F.L.; Patel, A.H.; Blum, H.E.; Baumert, T.F. Viral and cellular determinants of the hepatitis C virus envelope-heparan sulfate interaction. J. Virol.,  2006, 80(21), 10579-10590.
 [http://dx.doi.org/10.1128/JVI.00941-06] [PMID: 16928753]

[134]
Basu, A.; Kanda, T.; Beyene, A.; Saito, K.; Meyer, K.; Ray, R. Sulfated homologues of heparin inhibit hepatitis C virus entry into mammalian cells. J. Virol.,  2007, 81(8), 3933-3941.
 [http://dx.doi.org/10.1128/JVI.02622-06] [PMID: 17287282]

[135]
Kobayashi, F.; Yamada, S.; Taguwa, S.; Kataoka, C.; Naito, S.; Hama, Y.; Tani, H.; Matsuura, Y.; Sugahara, K. Specific interaction of the envelope glycoproteins E1 and E2 with liver heparan sulfate involved in the tissue tropismatic infection by hepatitis C virus. Glycoconj. J.,  2012, 29(4), 211-220.
 [http://dx.doi.org/10.1007/s10719-012-9388-z] [PMID: 22660965]

[136]
Jiang, J.; Cun, W.; Wu, X.; Shi, Q.; Tang, H.; Luo, G. Hepatitis C virus attachment mediated by apolipoprotein E binding to cell surface heparan sulfate. J. Virol.,  2012, 86(13), 7256-7267.
 [http://dx.doi.org/10.1128/JVI.07222-11] [PMID: 22532692]

[137]
Jiang, J.; Wu, X.; Tang, H.; Luo, G. Apolipoprotein E mediates attachment of clinical hepatitis C virus to hepatocytes by binding to cell surface heparan sulfate proteoglycan receptors. PLoS One,  2013, 8(7), e67982.
 [http://dx.doi.org/10.1371/journal.pone.0067982] [PMID: 23844141]

[138]
Xu, Y.; Martinez, P.; Séron, K.; Luo, G.; Allain, F.; Dubuisson, J.; Belouzard, S. Characterization of hepatitis C virus interaction with heparan sulfate proteoglycans. J. Virol.,  2015, 89(7), 3846-3858.
 [http://dx.doi.org/10.1128/JVI.03647-14] [PMID: 25609801]

[139]
Chavas, L.M.G.; Kato, R.; Suzuki, N.; von Itzstein, M.; Mann, M.C.; Thomson, R.J.; Dyason, J.C.; McKimm-Breschkin, J.; Fusi, P.; Tringali, C.; Venerando, B.; Tettamanti, G.; Monti, E.; Wakatsuki, S. Complexity in influenza virus targeted drug design: interaction with human sialidases. J. Med. Chem.,  2010, 53(7), 2998-3002.
 [http://dx.doi.org/10.1021/jm100078r] [PMID: 20222714]

[140]
Foni, E.; Chiapponi, C.; Baioni, L.; Zanni, I.; Merenda, M.; Rosignoli, C.; Kyriakis, C. S.; Luini, M. V.; Mandola, M. L.; Bolzoni, L.; Nigrelli, A. D.; Faccini, S. Influenza D in Italy: towards a better understanding of an emerging viral infection in swine. Sci. Rep.-Uk,  2017, 7(1), 11660.
 [http://dx.doi.org/10.1038/s41598-017-12012-3]

[141]
Skidmore, M.A.; Kajaste-Rudnitski, A.; Wells, N.M.; Guimond, S.E.; Rudd, T.R.; Yates, E.A.; Vicenzi, E. Inhibition of influenza H5N1 invasion by modified heparin derivatives. MedChemComm,  2015, 6(4), 640-646.
 [http://dx.doi.org/10.1039/C4MD00516C]

[142]
Lai, K.M.; Goh, B.H.; Lee, W.L. Attenuating influenza a virus infection by heparin binding EGF-like growth factor. Growth Factors,  2020, 38(3-4), 167-176.
 [http://dx.doi.org/10.1080/08977194.2021.1895144] [PMID: 33719806]

[143]
Levy, H.C.; Bowman, V.D.; Govindasamy, L.; McKenna, R.; Nash, K.; Warrington, K.; Chen, W.; Muzyczka, N.; Yan, X.; Baker, T.S.; Agbandje-McKenna, M. Heparin binding induces conformational changes in Adeno-associated virus serotype 2. J. Struct. Biol.,  2009, 165(3), 146-156.
 [http://dx.doi.org/10.1016/j.jsb.2008.12.002] [PMID: 19121398]

[144]
Walker, S.J.; Pizzato, M.; Takeuchi, Y.; Devereux, S. Heparin binds to murine leukemia virus and inhibits Env-independent attachment and infection. J. Virol.,  2002, 76(14), 6909-6918.
 [http://dx.doi.org/10.1128/JVI.76.14.6909-6918.2002] [PMID: 12072492]

[145]
Tanaka, A.; Tumkosit, U.; Nakamura, S.; Motooka, D.; Kishishita, N.; Priengprom, T.; Sa-ngasang, A.; Kinoshita, T.; Takeda, N.; Maeda, Y. Genome-wide screening uncovers the significance of N-sulfation of heparan sulfate as a host cell factor for chikungunya virus infection. J. Virol.,  2017, 91(13), e00432-17.
 [http://dx.doi.org/10.1128/JVI.00432-17] [PMID: 28404855]

[146]
Sahoo, B.; Chowdary, T.K. Conformational changes in Chikungunya virus E2 protein upon heparan sulfate receptor binding explain mechanism of E2–E1 dissociation during viral entry. Biosci. Rep.,  2019, 39(6), BSR20191077.
 [http://dx.doi.org/10.1042/BSR20191077] [PMID: 31167876]

[147]
McAllister, N.; Liu, Y.; Silva, L.M.; Lentscher, A.J.; Chai, W.; Wu, N.; Griswold, K.A.; Raghunathan, K.; Vang, L.; Alexander, J.; Warfield, K.L.; Diamond, M.S.; Feizi, T.; Silva, L.A.; Dermody, T.S. Chikungunya virus strains from each genetic clade bind sulfated glycosaminoglycans as attachment factors. J. Virol.,  2020, 94(24), e01500-20.
 [http://dx.doi.org/10.1128/JVI.01500-20] [PMID: 32999033]

[148]
Wu, S.; Wu, Z.; Wu, Y.; Wang, T.; Wang, M.; Jia, R.; Zhu, D.; Liu, M.; Zhao, X.; Yang, Q.; Wu, Y.; Zhang, S.; Liu, Y.; Zhang, L.; Yu, Y.; Pan, L.; Chen, S.; Cheng, A. Heparin sulfate is the attachment factor of duck Tembus virus on both BHK21 and DEF cells. Virol. J.,  2019, 16(1), 134.
 [http://dx.doi.org/10.1186/s12985-019-1246-1] [PMID: 31718685]

[149]
Salvador, B.; Sexton, N.R.; Carrion, R., Jr; Nunneley, J.; Patterson, J.L.; Steffen, I.; Lu, K.; Muench, M.O.; Lembo, D.; Simmons, G. Filoviruses utilize glycosaminoglycans for their attachment to target cells. J. Virol.,  2013, 87(6), 3295-3304.
 [http://dx.doi.org/10.1128/JVI.01621-12] [PMID: 23302881]

[150]
Tamhankar, M.; Gerhardt, D.M.; Bennett, R.S.; Murphy, N.; Jahrling, P.B.; Patterson, J.L. Heparan sulfate is an important mediator of Ebola virus infection in polarized epithelial cells. Virol. J.,  2018, 15(1), 135.
 [http://dx.doi.org/10.1186/s12985-018-1045-0] [PMID: 30165875]

[151]
Su, C.M.; Liao, C.L.; Lee, Y.L.; Lin, Y.L. Highly sulfated forms of heparin sulfate are involved in japanese encephalitis virus infection. Virology,  2001, 286(1), 206-215.
 [http://dx.doi.org/10.1006/viro.2001.0986] [PMID: 11448173]

[152]
Terao-Muto, Y.; Yoneda, M.; Seki, T.; Watanabe, A.; Tsukiyama-Kohara, K.; Fujita, K.; Kai, C. Heparin-like glycosaminoglycans prevent the infection of measles virus in SLAM-negative cell lines. Antiviral Res.,  2008, 80(3), 370-376.
 [http://dx.doi.org/10.1016/j.antiviral.2008.08.006] [PMID: 18812191]

[153]
Huan, C.; Wang, Y.; Ni, B.; Wang, R.; Huang, L.; Ren, X.; Tong, G.; Ding, C.; Fan, H.; Mao, X. Porcine epidemic diarrhea virus uses cell-surface heparan sulfate as an attachment factor. Arch. Virol.,  2015, 160(7), 1621-1628.
 [http://dx.doi.org/10.1007/s00705-015-2408-0] [PMID: 25896095]

[154]
Sasaki, M.; Anindita, P.D.; Ito, N.; Sugiyama, M.; Carr, M.; Fukuhara, H.; Ose, T.; Maenaka, K.; Takada, A.; Hall, W.W.; Orba, Y.; Sawa, H. The role of heparan sulfate proteoglycans as an attachment factor for rabies virus entry and infection. J. Infect. Dis.,  2018, 217(11), 1740-1749.
 [http://dx.doi.org/10.1093/infdis/jiy081] [PMID: 29529215]

[155]
Ke, F.; Wang, Z.H.; Ming, C.Y.; Zhang, Q.Y. Ranaviruses bind cells from different species through interaction with heparan sulfate. Viruses,  2019, 11(7), 593.
 [http://dx.doi.org/10.3390/v11070593] [PMID: 31261956]

[156]
Bear, J.S.; Byrnes, A.P.; Griffin, D.E. Heparin-binding and patterns of virulence for two recombinant strains of Sindbis virus. Virology,  2006, 347(1), 183-190.
 [http://dx.doi.org/10.1016/j.virol.2005.11.034] [PMID: 16380143]

[157]
Montanuy, I.; Alejo, A.; Alcami, A. Glycosaminoglycans mediate retention of the poxvirus type I interferon binding protein at the cell surface to locally block interferon antiviral responses. FASEB J.,  2011, 25(6), 1960-1971.
 [http://dx.doi.org/10.1096/fj.10-177188] [PMID: 21372110]

[158]
Banik, N.; Yang, S.B.; Kang, T.B.; Lim, J.H.; Park, J. Heparin and its derivatives: challenges and advances in therapeutic biomolecules. Int. J. Mol. Sci.,  2021, 22(19), 10524.
 [http://dx.doi.org/10.3390/ijms221910524] [PMID: 34638867]

[159]
Torres, F.G.; Troncoso, O.P.; Pisani, A.; Gatto, F.; Bardi, G. Natural polysaccharide nanomaterials: an overview of their immunological properties. Int. J. Mol. Sci.,  2019, 20(20), 5092.
 [http://dx.doi.org/10.3390/ijms20205092] [PMID: 31615111]

[160]
Qiu, X.L.; Fan, Z.R.; Liu, Y.Y.; Wang, D.F.; Wang, S.X.; Li, C.X. Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with heparin phospholipid complex. Int. J. Mol. Sci.,  2021, 22(8), 4077.
 [http://dx.doi.org/10.3390/ijms22084077] [PMID: 33920853]

[161]
Wan, X.; Li, P.; Jin, X.; Su, F.; Shen, J.; Yuan, J. Poly(ε- caprolactone)/keratin/heparin/VEGF biocomposite mats for vascular tissue engineering. J. Biomed. Mater. Res. A,  2020, 108(2), 292-300.
 [http://dx.doi.org/10.1002/jbm.a.36815] [PMID: 31606923]

[162]
Pitt, E.A.; Dogra, P.; Patel, R.S.; Williams, A.; Wall, J.S.; Sparer, T.E. The D-form of a novel heparan binding peptide decreases cytomegalovirus infection in vivo and in vitro. Antiviral Res.,  2016, 135, 15-23.
 [http://dx.doi.org/10.1016/j.antiviral.2016.09.012] [PMID: 27678155]

[163]
Hondermarck, H.; Bartlett, N.W.; Nurcombe, V. The role of growth factor receptors in viral infections: An opportunity for drug repurposing against emerging viral diseases such as COVID-19? FASEB Bioadv.,  2020, 2(5), 296-303.
 [http://dx.doi.org/10.1096/fba.2020-00015] [PMID: 32395702]

[164]
Häcker, U.; Nybakken, K.; Perrimon, N. Heparan sulphate proteoglycans: the sweet side of development. Nat. Rev. Mol. Cell Biol.,  2005, 6(7), 530-541.
 [http://dx.doi.org/10.1038/nrm1681] [PMID: 16072037]

[165]
Chen, D. Heparin beyond anti-coagulation. Curr. Res. Transl. Med.,  2021, 69(4), 103300-103303.
 [http://dx.doi.org/10.1016/j.retram.2021.103300] [PMID: 34237474]

[166]
Goldberg, M.; Gomez-Orellana, I. Challenges for the oral delivery of macromolecules. Nat. Rev. Drug Discov.,  2003, 2(4), 289-295.
 [http://dx.doi.org/10.1038/nrd1067] [PMID: 12669028]

[167]
Schlüter, A.; Lamprecht, A. Current developments for the oral delivery of heparin. Curr. Pharm. Biotechnol.,  2014, 15(7), 640-649.
 [http://dx.doi.org/10.2174/1389201015666140915151649] [PMID: 25219865]

[168]
Fang, G.; Tang, B. Advanced delivery strategies facilitating oral absorption of heparins. Asian J. Pharmaceut. Sci.,  2020, 15(4), 449-460.
 [http://dx.doi.org/10.1016/j.ajps.2019.11.006] [PMID: 32952668]

[169]
Wat, J.M.; Hawrylyshyn, K.; Baczyk, D.; Greig, I.R.; Kingdom, J.C. Effects of glycol-split low molecular weight heparin on placental, endothelial, and anti-inflammatory pathways relevant to preeclampsia. Biol. Reprod.,  2018, 99(5), 1082-1090.
 [http://dx.doi.org/10.1093/biolre/ioy127] [PMID: 29860275]

[170]
Yu, M.; Zhang, T.; Zhang, W.; Sun, Q.; Li, H.; Li, J. 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. Mol. Biosci.,  2021, 7, 628551-628563.
 [http://dx.doi.org/10.3389/fmolb.2020.628551] [PMID: 33569392]
Cite As
Current Medicinal Chemistry

Research Progress on Antiviral Activity of Heparin

Abstract
