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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Review Article

Isopeptide Bond Bundling Superhelix for Designing Antivirals against Enveloped Viruses with Class I Fusion Proteins: A Review

Author(s): Heiya Na, Guodong Liang* and Wenqing Lai*

Volume 24, Issue 14, 2023

Published on: 18 April, 2023

Page: [1774 - 1783] Pages: 10

DOI: 10.2174/1389201024666230330083640

Price: $65

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Abstract

Viral infection has become one of the worst human lethal diseases. In recent years, major gains have been made in the research of peptide-based antiviral agents on account of the mechanism of viral membrane fusion, among which the peptide Enfuvirtide has been listed for the treatment of AIDS. This paper reviewed a new way to design peptide-based antiviral agents by "bundling" superhelix with isopeptide bonds to construct the active advanced structure. It can solve the problem that peptide precursor compounds derived from the natural sequence of viral envelope protein tend to aggregate and precipitate under physiological conditions and low activity and endow the peptide agents with the feature of thermal stability, protease stability and in vitro metabolic stability. This approach is also providing a new way of thinking for the research and development of broad-spectrum peptide-based antiviral agents.

Keywords: Peptide-based antiviral agents, superhelix, isopeptide bond, viral fusion, compounds, isopeptide.

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[1]
Seley-Radtke, K.L.; Thames, J.E.; Waters, C.D. III Broad spectrum antiviral nucleosides-Our best hope for the future. Annu. Rep. Med. Chem., 2021, 57, 109-132.
[http://dx.doi.org/10.1016/bs.armc.2021.09.001] [PMID: 34728865]
[2]
Vigant, F.; Santos, N.C.; Lee, B. Broad-spectrum antivirals against viral fusion. Nat. Rev. Microbiol., 2015, 13(7), 426-437.
[http://dx.doi.org/10.1038/nrmicro3475] [PMID: 26075364]
[3]
Pattnaik, G.P.; Chakraborty, H. Entry inhibitors: efficient means to block viral infection. J. Membr. Biol., 2020, 253(5), 425-444.
[http://dx.doi.org/10.1007/s00232-020-00136-z] [PMID: 32862236]
[4]
Dimitrov, D.S. Virus entry: Molecular mechanisms and biomedical applications. Nat. Rev. Microbiol., 2004, 2(2), 109-122.
[http://dx.doi.org/10.1038/nrmicro817] [PMID: 15043007]
[5]
Wyatt, R.; Sodroski, J. The HIV-1 envelope glycoproteins: Fusogens, antigens, and immunogens. Science, 1998, 280(5371), 1884-1888.
[http://dx.doi.org/10.1126/science.280.5371.1884] [PMID: 9632381]
[6]
Harrison, S.C. Mechanism of membrane fusion by viral envelope proteins. Adv. Virus Res., 2005, 64, 231-261.
[http://dx.doi.org/10.1016/S0065-3527(05)64007-9] [PMID: 16139596]
[7]
Düzgüneş, N.; Fernandez-Fuentes, N.; Konopka, K. Inhibition of viral membrane fusion by peptides and approaches to peptide design. Pathogens, 2021, 10(12), 1599.
[http://dx.doi.org/10.3390/pathogens10121599] [PMID: 34959554]
[8]
Schütz, D.; Ruiz-Blanco, Y.B.; Münch, J.; Kirchhoff, F.; Sanchez-Garcia, E.; Müller, J.A. Peptide and peptide-based inhibitors of SARS-CoV-2 entry. Adv. Drug Deliv. Rev., 2020, 167, 47-65.
[http://dx.doi.org/10.1016/j.addr.2020.11.007] [PMID: 33189768]
[9]
Jiang, S.; Zhang, X.; Du, L. Therapeutic antibodies and fusion inhibitors targeting the spike protein of SARS-CoV-2. Expert Opin. Ther. Targets, 2021, 25(6), 415-421.
[http://dx.doi.org/10.1080/14728222.2020.1820482] [PMID: 32941780]
[10]
Xiao, T.; Cai, Y.; Chen, B. HIV-1 entry and membrane fusion inhibitors. Viruses, 2021, 13(5), 735.
[http://dx.doi.org/10.3390/v13050735] [PMID: 33922579]
[11]
Barrett, C.T.; Dutch, R.E. Viral membrane fusion and the transmembrane domain. Viruses, 2020, 12(7), 693.
[http://dx.doi.org/10.3390/v12070693] [PMID: 32604992]
[12]
Wang, H.; Wang, C. Peptide-based dual HIV and coronavirus entry inhibitors. Adv. Exp. Med. Biol., 2022, 1366, 87-100.
[http://dx.doi.org/10.1007/978-981-16-8702-0_6] [PMID: 35412136]
[13]
White, J.M.; Whittaker, G.R. Fusion of enveloped viruses in endosomes. Traffic, 2016, 17(6), 593-614.
[http://dx.doi.org/10.1111/tra.12389] [PMID: 26935856]
[14]
Pu, J.; Zhou, J.T.; Liu, P.; Yu, F.; He, X.; Lu, L.; Jiang, S. Viral entry inhibitors targeting six-helical bundle core against highly pathogenic enveloped viruses with class I fusion proteins. Curr. Med. Chem., 2022, 29(4), 700-718.
[http://dx.doi.org/10.2174/0929867328666210511015808] [PMID: 33992055]
[15]
Harrison, S.C. Viral membrane fusion. Virology, 2015, 479-480, 498-507.
[http://dx.doi.org/10.1016/j.virol.2015.03.043] [PMID: 25866377]
[16]
Harrison, J.S.; Higgins, C.D.; O’Meara, M.J.; Koellhoffer, J.F.; Kuhlman, B.A.; Lai, J.R. Role of electrostatic repulsion in controlling pH-dependent conformational changes of viral fusion proteins. Structure, 2013, 21(7), 1085-1096.
[http://dx.doi.org/10.1016/j.str.2013.05.009] [PMID: 23823327]
[17]
Carr, C.M.; Kim, P.S. A spring-loaded mechanism for the conformational change of influenza hemagglutinin. Cell, 1993, 73(4), 823-832.
[http://dx.doi.org/10.1016/0092-8674(93)90260-W] [PMID: 8500173]
[18]
Clinton, T.R.; Weinstock, M.T.; Jacobsen, M.T.; Szabo-Fresnais, N.; Pandya, M.J.; Whitby, F.G.; Herbert, A.S.; Prugar, L.I.; McKinnon, R.; Hill, C.P.; Welch, B.D.; Dye, J.M.; Eckert, D.M.; Kay, M.S. Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets. Protein Sci., 2015, 24(4), 446-463.
[http://dx.doi.org/10.1002/pro.2578] [PMID: 25287718]
[19]
Eckert, D.M.; Kim, P.S. Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region. Proc. Natl. Acad. Sci., 2001, 98(20), 11187-11192.
[http://dx.doi.org/10.1073/pnas.201392898] [PMID: 11572974]
[20]
Matthews, J.M.; Young, T.F.; Tucker, S.P.; Mackay, J.P. The core of the respiratory syncytial virus fusion protein is a trimeric coiled coil. J. Virol., 2000, 74(13), 5911-5920.
[http://dx.doi.org/10.1128/JVI.74.13.5911-5920.2000] [PMID: 10846072]
[21]
Zheng, X.; Liang, G.; Wang, C.; Liu, K. Construction of isopeptide bridge-tethered NHR-trimeric coiled-coil in MERS-CoV membrane fusion protein. Chem. J. Chin. Univ., 2016, 37(9), 1643-1648.
[22]
Zhang, L.; Huang, Y.; He, T.; Cao, Y.; Ho, D.D. HIV-1 subtype and second-receptor use. Nature, 1996, 383(6603), 768.
[http://dx.doi.org/10.1038/383768a0] [PMID: 8892998]
[23]
Jing, S.; Zhao, Q.; Debnath, A. Peptide and non-peptide HIV fusion inhibitors. Curr. Pharm. Des., 2002, 8(8), 563-580.
[http://dx.doi.org/10.2174/1381612024607180] [PMID: 11945159]
[24]
Ivankin, A.; Apellániz, B.; Gidalevitz, D.; Nieva, J.L. Mechanism of membrane perturbation by the HIV-1 gp41 membrane-proximal external region and its modulation by cholesterol. Biochim. Biophys. Acta Biomembr., 2012, 1818(11), 2521-2528.
[http://dx.doi.org/10.1016/j.bbamem.2012.06.002] [PMID: 22692008]
[25]
Bewley, C.A.; Louis, J.M.; Ghirlando, R.; Clore, G.M. Design of a novel peptide inhibitor of HIV fusion that disrupts the internal trimeric coiled-coil of gp41. J. Biol. Chem., 2002, 277(16), 14238-14245.
[http://dx.doi.org/10.1074/jbc.M201453200] [PMID: 11859089]
[26]
Chen, X.; Lu, L.; Qi, Z.; Lu, H.; Wang, J.; Yu, X.; Chen, Y.; Jiang, S. Novel recombinant engineered gp41 N-terminal heptad repeat trimers and their potential as anti-HIV-1 therapeutics or microbicides. J. Biol. Chem., 2010, 285(33), 25506-25515.
[http://dx.doi.org/10.1074/jbc.M110.101170] [PMID: 20538590]
[27]
Nyakatura, E.K.; Frei, J.C.; Lai, J.R. Chemical and structural aspects of ebola virus entry inhibitors. ACS Infect. Dis., 2015, 1(1), 42-52.
[http://dx.doi.org/10.1021/id500025n] [PMID: 25984565]
[28]
Liu, I.J.; Kao, C.L.; Hsieh, S.C.; Wey, M.T.; Kan, L.S.; Wang, W.K. Identification of a minimal peptide derived from heptad repeat (HR) 2 of spike protein of SARS-CoV and combination of HR1-derived peptides as fusion inhibitors. Antiviral Res., 2009, 81(1), 82-87.
[http://dx.doi.org/10.1016/j.antiviral.2008.10.001] [PMID: 18983873]
[29]
Louis, J.M.; Nesheiwat, I.; Chang, L.; Clore, G.M.; Bewley, C.A. Covalent trimers of the internal N-terminal trimeric coiled-coil of gp41 and antibodies directed against them are potent inhibitors of HIV envelope-mediated cell fusion. J. Biol. Chem., 2003, 278(22), 20278-20285.
[http://dx.doi.org/10.1074/jbc.M301627200] [PMID: 12654905]
[30]
Bianchi, E.; Finotto, M.; Ingallinella, P.; Hrin, R.; Carella, A.V.; Hou, X.S.; Schleif, W.A.; Miller, M.D.; Geleziunas, R.; Pessi, A. Covalent stabilization of coiled coils of the HIV gp41 N region yields extremely potent and broad inhibitors of viral infection. Proc. Natl. Acad. Sci., 2005, 102(36), 12903-12908.
[http://dx.doi.org/10.1073/pnas.0502449102] [PMID: 16129831]
[31]
Brülisauer, L.; Gauthier, M.A.; Leroux, J.C. Disulfide-containing parenteral delivery systems and their redox-biological fate. J. Control. Release, 2014, 195, 147-154.
[http://dx.doi.org/10.1016/j.jconrel.2014.06.012] [PMID: 24952369]
[32]
Kang, H.J.; Coulibaly, F.; Clow, F.; Proft, T.; Baker, E.N. Stabilizing isopeptide bonds revealed in gram-positive bacterial pilus structure. Science, 2007, 318(5856), 1625-1628.
[http://dx.doi.org/10.1126/science.1145806] [PMID: 18063798]
[33]
Zakeri, B.; Fierer, J.O.; Celik, E.; Chittock, E.C.; Schwarz-Linek, U.; Moy, V.T.; Howarth, M. Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin. Proc. Natl. Acad. Sci., 2012, 109(12), E690-E697.
[http://dx.doi.org/10.1073/pnas.1115485109] [PMID: 22366317]
[34]
Fierer, J.O.; Veggiani, G.; Howarth, M. SpyLigase peptide–peptide ligation polymerizes affibodies to enhance magnetic cancer cell capture. Proc. Natl. Acad. Sci. USA, 2014, 111(13), E1176-E1181.
[http://dx.doi.org/10.1073/pnas.1315776111] [PMID: 24639550]
[35]
Brune, K.D.; Leneghan, D.B.; Brian, I.J.; Ishizuka, A.S.; Bachmann, M.F.; Draper, S.J.; Biswas, S.; Howarth, M. Plug-and-display: decoration of virus-like particles via isopeptide bonds for modular immunization. Sci. Rep., 2016, 6(1), 19234.
[http://dx.doi.org/10.1038/srep19234] [PMID: 26781591]
[36]
Zakeri, B.; Howarth, M. Spontaneous intermolecular amide bond formation between side chains for irreversible peptide targeting. J. Am. Chem. Soc., 2010, 132(13), 4526-4527.
[http://dx.doi.org/10.1021/ja910795a] [PMID: 20235501]
[37]
Fletcher, J.M.; Boyle, A.L.; Bruning, M.; Bartlett, G.J.; Vincent, T.L.; Zaccai, N.R.; Armstrong, C.T.; Bromley, E.H.C.; Booth, P.J.; Brady, R.L.; Thomson, A.R.; Woolfson, D.N. A basis set of de novo coiled-coil peptide oligomers for rational protein design and synthetic biology. ACS Synth. Biol., 2012, 1(6), 240-250.
[http://dx.doi.org/10.1021/sb300028q] [PMID: 23651206]
[38]
Bai, Y.; Xue, H.; Ling, Y.; Cheng, M.; Cai, L.; Liu, K. Inter-chain acyl transfer reaction in a peptide six-helical bundle: A chemical method for regulating the interaction between peptides or proteins. Chem. Commun., 2012, 48(36), 4320-4322.
[http://dx.doi.org/10.1039/c2cc17428f] [PMID: 22451895]
[39]
Bai, Y.; Wang, C.; Liang, G.; Lai, W.; Xue, H.; Ling, Y.; Cheng, M.; Liu, K. Precisely designed isopeptide bridge-crosslinking endows artificial hydrolases with high stability and catalytic activity under extreme denaturing conditions. Chem. Asian J., 2017, 12(19), 2539-2543.
[http://dx.doi.org/10.1002/asia.201701021] [PMID: 28742253]
[40]
Wang, C.; Lai, W.; Yu, F.; Zhang, T.; Lu, L.; Jiang, X.; Zhang, Z.; Xu, X.; Bai, Y.; Jiang, S.; Liu, K. De novo design of isopeptide bond-tethered triple-stranded coiled coils with exceptional resistance to unfolding and proteolysis: Implication for developing antiviral therapeutics. Chem. Sci., 2015, 6(11), 6505-6509.
[http://dx.doi.org/10.1039/C5SC02220G] [PMID: 30090269]
[41]
Lai, W.; Wang, C.; Yan, J.; Liu, H.; Zhang, W.; Lin, B.; Xi, Z. Suitable fusion of N-terminal heptad repeats to achieve covalently stabilized potent N-peptide inhibitors of HIV-1 infection. Bioorg. Med. Chem., 2020, 28(4), 115214.
[http://dx.doi.org/10.1016/j.bmc.2019.115214] [PMID: 31932193]
[42]
Wang, C.; Li, X.; Yu, F.; Lu, L.; Jiang, X.; Xu, X.; Wang, H.; Lai, W.; Zhang, T.; Zhang, Z.; Ye, L.; Jiang, S.; Liu, K. Site-specific isopeptide bridge tethering of chimeric gp41 n-terminal heptad repeat helical trimers for the treatment of HIV-1 Infection. Sci. Rep., 2016, 6(1), 32161.
[http://dx.doi.org/10.1038/srep32161] [PMID: 27562370]
[43]
Chan, D.C.; Fass, D.; Berger, J.M.; Kim, P.S. Core structure of gp41 from the HIV envelope glycoprotein. Cell, 1997, 89(2), 263-273.
[http://dx.doi.org/10.1016/S0092-8674(00)80205-6] [PMID: 9108481]
[44]
Lai, W.; Wang, C.; Yu, F.; Lu, L.; Wang, Q.; Jiang, X.; Xu, X.; Zhang, T.; Wu, S.; Zheng, X.; Zhang, Z.; Dong, F.; Jiang, S.; Liu, K. An effective strategy for recapitulating N-terminal heptad repeat trimers in enveloped virus surface glycoproteins for therapeutic applications. Chem. Sci., 2016, 7(3), 2145-2150.
[http://dx.doi.org/10.1039/C5SC04046A] [PMID: 29899942]
[45]
Li, X.; Lai, W.; Jiang, X.; Wang, C.; Liu, KL. Design, synthesis and activity screening of isopeptide bond-tethered N peptides as HIV-1 fusion inhibitors. Chem. J. Chin. Univ., 2016, 37(5), 881-885.
[46]
Ernst, J.T.; Kutzki, O.; Debnath, A.K.; Jiang, S.; Lu, H.; Hamilton, A.D. Design of a protein surface antagonist based on alpha-helix mimicry: Inhibition of gp41 assembly and viral fusion. Angew. Chem. Int. Ed., 2002, 41(2), 278-281.
[http://dx.doi.org/10.1002/1521-3773(20020118)41:2<278:AID-ANIE278>3.0.CO;2-A] [PMID: 12491408]
[47]
Apostolovic, B.; Danial, M.; Klok, H.A. Coiled coils: Attractive protein folding motifs for the fabrication of self-assembled, responsive and bioactive materials. Chem. Soc. Rev., 2010, 39(9), 3541-3575.
[http://dx.doi.org/10.1039/b914339b] [PMID: 20676430]
[48]
Fletcher, J.M.; Horner, K.A.; Bartlett, G.J.; Rhys, G.G.; Wilson, A.J.; Woolfson, D.N. De novo coiled-coil peptides as scaffolds for disrupting protein–protein interactions. Chem. Sci., 2018, 9(39), 7656-7665.
[http://dx.doi.org/10.1039/C8SC02643B] [PMID: 30393526]
[49]
Wang, C.; Xia, S.; Wang, X.; Li, Y.; Wang, H.; Xiang, R.; Jiang, Q.; Lan, Q.; Liang, R.; Li, Q.; Huo, S.; Lu, L.; Wang, Q.; Yu, F.; Liu, K.; Jiang, S. Supercoiling structure-based design of a trimeric coiled-coil peptide with high potency against HIV-1 and human β-coronavirus infection. J. Med. Chem., 2022, 65(4), 2809-2819.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00258] [PMID: 33929200]
[50]
Heydari, H.; Golmohammadi, R.; Mirnejad, R.; Tebyanian, H.; Fasihi-Ramandi, M.; Moosazadeh Moghaddam, M. Antiviral peptides against Coronaviridae family: A review. Peptides, 2021, 139, 170526.
[http://dx.doi.org/10.1016/j.peptides.2021.170526] [PMID: 33676968]
[51]
Bode, S.A.; Kruis, I.C.; Adams, H.P.J.H.M.; Boelens, W.C.; Pruijn, G.J.M.; van Hest, J.C.M.; Löwik, D.W.P.M. Coiled-coil-mediated activation of oligoarginine cell-penetrating peptides. Chem. Bio. Chem., 2017, 18(2), 185-188.
[http://dx.doi.org/10.1002/cbic.201600614] [PMID: 27870530]
[52]
Gump, J.M.; Dowdy, S.F. TAT transduction: The molecular mechanism and therapeutic prospects. Trends Mol. Med., 2007, 13(10), 443-448.
[http://dx.doi.org/10.1016/j.molmed.2007.08.002] [PMID: 17913584]
[53]
Xia, S.; Zhu, Y.; Liu, M.; Lan, Q.; Xu, W.; Wu, Y.; Ying, T.; Liu, S.; Shi, Z.; Jiang, S.; Lu, L. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell. Mol. Immunol., 2020, 17(7), 765-767.
[http://dx.doi.org/10.1038/s41423-020-0374-2] [PMID: 32047258]
[54]
Xia, S.; Liu, M.; Wang, C.; Xu, W.; Lan, Q.; Feng, S.; Qi, F.; Bao, L.; Du, L.; Liu, S.; Qin, C.; Sun, F.; Shi, Z.; Zhu, Y.; Jiang, S.; Lu, L. Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res., 2020, 30(4), 343-355.
[http://dx.doi.org/10.1038/s41422-020-0305-x] [PMID: 32231345]

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