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Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Mini-Review Article

Fusion Protein Targeted Antiviral Peptides: Fragment-Based Drug Design (FBDD) Guided Rational Design of Dipeptides Against SARS-CoV-2

Author(s): Sounik Manna, Trinath Chowdhury, Piyush Baindara and Santi M. Mandal*

Volume 21, Issue 10, 2020

Page: [938 - 947] Pages: 10

DOI: 10.2174/1389203721666200908164641

Price: $65

Abstract

Infectious diseases caused by viruses have become a serious public health issue in the recent past, including the current pandemic situation of COVID-19. Enveloped viruses are most commonly known to cause emerging and recurring infectious diseases. Viral and cell membrane fusion is the major key event in the case of enveloped viruses that is required for their entry into the cell. Viral fusion proteins play an important role in the fusion process and in infection establishment. Because of this, the fusion process targeting antivirals become an interest to fight against viral diseases caused by the enveloped virus. Lower respiratory tract infections casing viruses like influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus (SARS-CoV) are examples of such enveloped viruses that are at the top in public health issues. Here, we summarized the viral fusion protein targeted antiviral peptides along with their mechanism and specific design to combat the viral fusion process. The pandemic COVID-19, severe respiratory syndrome disease is an outbreak worldwide. There are no definitive drugs yet, but few are in on-going trials. Here, an approach of fragmentbased drug design (FBDD) methodology is used to identify the broad spectrum agent target to the conserved region of fusion protein of SARS CoV-2. Three dipeptides (DL, LQ and ID) were chosen from the library and designed by the systematic combination along with their possible modifications of amino acids to the target sites. Designed peptides were docked with targeted fusion protein after energy minimization. Results show strong and significant binding affinity (DL = -60.1 kcal/mol; LQ = - 62.8 kcal/mol; ID= -71.5 kcal/mol) during interaction. Anyone of the active peptides from the developed libraries may help to block the target sites competitively to successfully control COVID-19.

Keywords: Viral infections, enveloped viruses, fusion protein, antiviral peptides, FBDD, SARS-CoV-2.

Graphical Abstract

[1]
De Clercq, E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int. J. Antimicrob. Agents, 2009, 33(4), 307-320.
[http://dx.doi.org/10.1016/j.ijantimicag.2008.10.010] [PMID: 19108994]
[2]
Lacombe, K.; Rockstroh, J. HIV and viral hepatitis coinfections: advances and challenges. Gut, 2012, 61(Suppl. 1), i47-i58.
[http://dx.doi.org/10.1136/gutjnl-2012-302062] [PMID: 22504919]
[3]
Yen, H.L. Current and novel antiviral strategies for influenza infection. Curr. Opin. Virol., 2016, 18, 126-134.
[http://dx.doi.org/10.1016/j.coviro.2016.05.004] [PMID: 27344481]
[4]
Zhu, J.D.; Meng, W.; Wang, X.J.; Wang, H.C.R. Broad-spectrum antiviral agents. Front. Microbiol., 2015, 6, 517.
[http://dx.doi.org/10.3389/fmicb.2015.00517] [PMID: 26052325]
[5]
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]
[6]
Harrison, S.C. Viral membrane fusion. Nat. Struct. Mol. Biol., 2008, 15(7), 690-698.
[http://dx.doi.org/10.1038/nsmb.1456] [PMID: 18596815]
[7]
Vilas Boas, L.C.P.; Campos, M.L.; Berlanda, R.L.A.; de Carvalho Neves, N.; Franco, O.L. Antiviral peptides as promising therapeutic drugs. Cell. Mol. Life Sci., 2019, 76(18), 3525-3542.
[http://dx.doi.org/10.1007/s00018-019-03138-w] [PMID: 31101936]
[8]
Badani, H.; Garry, R.F.; Wimley, W.C. Peptide entry inhibitors of enveloped viruses: the importance of interfacial hydrophobicity. Biochim. Biophys. Acta, 2014, 1838(9), 2180-2197.
[http://dx.doi.org/10.1016/j.bbamem.2014.04.015] [PMID: 24780375]
[9]
Colman, P.M.; Lawrence, M.C. The structural biology of type I viral membrane fusion. Nat. Rev. Mol. Cell Biol., 2003, 4(4), 309-319.
[http://dx.doi.org/10.1038/nrm1076] [PMID: 12671653]
[10]
Wang, C.; Shi, W.; Cai, L.; Lu, L.; Yu, F.; Wang, Q.; Jiang, X.; Xu, X.; Wang, K.; Xu, L.; Jiang, S.; Liu, K. Artificial peptides conjugated with cholesterol and pocket-specific small molecules potently inhibit infection by laboratory-adapted and primary HIV-1 isolates and enfuvirtide-resistant HIV-1 strains. J. Antimicrob. Chemother., 2014, 69(6), 1537-1545.
[http://dx.doi.org/10.1093/jac/dku010] [PMID: 24500189]
[11]
Lee, K.K.; Pessi, A.; Gui, L.; Santoprete, A.; Talekar, A.; Moscona, A.; Porotto, M. Capturing a fusion intermediate of influenza hemagglutinin with a cholesterol-conjugated peptide, a new antiviral strategy for influenza virus. J. Biol. Chem., 2011, 286(49), 42141-42149.
[http://dx.doi.org/10.1074/jbc.M111.254243] [PMID: 21994935]
[12]
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. (Camb.), 2015, 6(11), 6505-6509.
[http://dx.doi.org/10.1039/C5SC02220G] [PMID: 30090269]
[13]
Wang, C.; Shi, W.; Cai, L.; Lu, L.; Wang, Q.; Zhang, T.; Li, J.; Zhang, Z.; Wang, K.; Xu, L.; Jiang, X.; Jiang, S.; Liu, K. Design, synthesis, and biological evaluation of highly potent small molecule-peptide conjugates as new HIV-1 fusion inhibitors. J. Med. Chem., 2013, 56(6), 2527-2539.
[http://dx.doi.org/10.1021/jm3018964] [PMID: 23458727]
[14]
Qi, Q.; Wang, Q.; Chen, W.; Du, L.; Dimitrov, D.S.; Lu, L.; Jiang, S. HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions. Emerg. Microbes Infect., 2017, 6(6)e59
[http://dx.doi.org/10.1038/emi.2017.46] [PMID: 28634358]
[15]
Lu, L.; Liu, Q.; Zhu, Y.; Chan, K.H.; Qin, L.; Li, Y.; Wang, Q.; Chan, J.F.; Du, L.; Yu, F.; Ma, C.; Ye, S.; Yuen, K.Y.; Zhang, R.; Jiang, S. Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor. Nat. Commun., 2014, 5, 3067.
[http://dx.doi.org/10.1038/ncomms4067] [PMID: 24473083]
[16]
Miller, E.H.; Harrison, J.S.; Radoshitzky, S.R.; Higgins, C.D.; Chi, X.; Dong, L.; Kuhn, J.H.; Bavari, S.; Lai, J.R.; Chandran, K. Inhibition of Ebola virus entry by a C-peptide targeted to endosomes. J. Biol. Chem., 2011, 286(18), 15854-15861.
[http://dx.doi.org/10.1074/jbc.M110.207084] [PMID: 21454542]
[17]
White, J.M.; Delos, S.E.; Brecher, M.; Schornberg, K. Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Crit. Rev. Biochem. Mol. Biol., 2008, 43(3), 189-219.
[http://dx.doi.org/10.1080/10409230802058320] [PMID: 18568847]
[18]
Pessi, A.; Langella, A.; Capitò, E.; Ghezzi, S.; Vicenzi, E.; Poli, G.; Ketas, T.; Mathieu, C.; Cortese, R.; Horvat, B.; Moscona, A.; Porotto, M. A general strategy to endow natural fusion-protein-derived peptides with potent antiviral activity. PLoS One, 2012, 7(5)e36833
[http://dx.doi.org/10.1371/journal.pone.0036833] [PMID: 22666328]
[19]
Ingallinella, P.; Bianchi, E.; Ladwa, N.A.; Wang, Y.J.; Hrin, R.; Veneziano, M.; Bonelli, F.; Ketas, T.J.; Moore, J.P.; Miller, M.D.; Pessi, A. Addition of a cholesterol group to an HIV-1 peptide fusion inhibitor dramatically increases its antiviral potency. Proc. Natl. Acad. Sci. USA, 2009, 106(14), 5801-5806.
[http://dx.doi.org/10.1073/pnas.0901007106] [PMID: 19297617]
[20]
Kielian, M. Class II virus membrane fusion proteins. Virology, 2006, 344(1), 38-47.
[http://dx.doi.org/10.1016/j.virol.2005.09.036] [PMID: 16364734]
[21]
Kielian, M.; Rey, F.A. Virus membrane-fusion proteins: more than one way to make a hairpin. Nat. Rev. Microbiol., 2006, 4(1), 67-76.
[http://dx.doi.org/10.1038/nrmicro1326] [PMID: 16357862]
[22]
Backovic, M.; Jardetzky, T.S. Class III viral membrane fusion proteins. Curr. Opin. Struct. Biol., 2009, 19(2), 189-196.
[http://dx.doi.org/10.1016/j.sbi.2009.02.012] [PMID: 19356922]
[23]
Lamb, R.A.; Jardetzky, T.S. Structural basis of viral invasion: lessons from paramyxovirus F. Curr. Opin. Struct. Biol., 2007, 17(4), 427-436.
[http://dx.doi.org/10.1016/j.sbi.2007.08.016] [PMID: 17870467]
[24]
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]
[25]
Mothes, W.; Boerger, A.L.; Narayan, S.; Cunningham, J.M.; Young, J.A.T. Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein. Cell, 2000, 103(4), 679-689.
[http://dx.doi.org/10.1016/S0092-8674(00)00170-7] [PMID: 11106737]
[26]
Narayan, S.; Barnard, R.J.O.; Young, J.A.T. Two retroviral entry pathways distinguished by lipid raft association of the viral receptor and differences in viral infectivity. J. Virol., 2003, 77(3), 1977-1983.
[http://dx.doi.org/10.1128/JVI.77.3.1977-1983.2003] [PMID: 12525631]
[27]
Thorley, J.A.; McKeating, J.A.; Rappoport, J.Z. Mechanisms of viral entry: sneaking in the front door. Protoplasma, 2010, 244(1-4), 15-24.
[http://dx.doi.org/10.1007/s00709-010-0152-6] [PMID: 20446005]
[28]
Plemper, R.K. Cell entry of enveloped viruses. Curr. Opin. Virol., 2011, 1(2), 92-100.
[http://dx.doi.org/10.1016/j.coviro.2011.06.002] [PMID: 21927634]
[29]
Albertini, A.; Bressanelli, S.; Lepault, J.; Gaudin, Y. Structure and working of viral fusion machinery. Curr. Top. Membr., 2011, 68, 49-80.
[http://dx.doi.org/10.1016/B978-0-12-385891-7.00003-9] [PMID: 21771495]
[30]
Ascough, S.; Paterson, S.; Chiu, C. Induction and subversion of human protective immunity: Contrasting influenza and respiratory syncytial virus. Front. Immunol., 2018, 9, 323.
[http://dx.doi.org/10.3389/fimmu.2018.00323] [PMID: 29552008]
[31]
Weissenhorn, W.; Hinz, A.; Gaudin, Y. Virus membrane fusion. FEBS Lett., 2007, 581(11), 2150-2155.
[http://dx.doi.org/10.1016/j.febslet.2007.01.093] [PMID: 17320081]
[32]
White, J.M. The first family of cell-cell fusion. Dev. Cell, 2007, 12(5), 667-668.
[http://dx.doi.org/10.1016/j.devcel.2007.04.009] [PMID: 17488618]
[33]
Moscona, A.; Peluso, R.W. Fusion properties of cells persistently infected with human parainfluenza virus type 3: participation of hemagglutinin-neuraminidase in membrane fusion. J. Virol., 1991, 65(6), 2773-2777.
[http://dx.doi.org/10.1128/JVI.65.6.2773-2777.1991] [PMID: 1851852]
[34]
Porotto, M.; Murrell, M.; Greengard, O.; Doctor, L.; Moscona, A. Influence of the human parainfluenza virus 3 attachment protein’s neuraminidase activity on its capacity to activate the fusion protein. J. Virol., 2005, 79(4), 2383-2392.
[http://dx.doi.org/10.1128/JVI.79.4.2383-2392.2005] [PMID: 15681439]
[35]
Porotto, M.; Murrell, M.; Greengard, O.; Moscona, A. Triggering of human parainfluenza virus 3 fusion protein (F) by the hemagglutinin-neuraminidase (HN) protein: an HN mutation diminishes the rate of F activation and fusion. J. Virol., 2003, 77(6), 3647-3654.
[http://dx.doi.org/10.1128/JVI.77.6.3647-3654.2003] [PMID: 12610140]
[36]
Cianci, C.; Yu, K.L.; Combrink, K.; Sin, N.; Pearce, B.; Wang, A.; Civiello, R.; Voss, S.; Luo, G.; Kadow, K.; Genovesi, E.V.; Venables, B.; Gulgeze, H.; Trehan, A.; James, J.; Lamb, L.; Medina, I.; Roach, J.; Yang, Z.; Zadjura, L.; Colonno, R.; Clark, J.; Meanwell, N.; Krystal, M. Orally active fusion inhibitor of respiratory syncytial virus. Antimicrob. Agents Chemother., 2004, 48(2), 413-422.
[http://dx.doi.org/10.1128/AAC.48.2.413-422.2004] [PMID: 14742189]
[37]
Cianci, C.; Langley, D.R.; Dischino, D.D.; Sun, Y.; Yu, K.L.; Stanley, A.; Roach, J.; Li, Z.; Dalterio, R.; Colonno, R.; Meanwell, N.A.; Krystal, M. Targeting a binding pocket within the trimer-of-hairpins: small-molecule inhibition of viral fusion. Proc. Natl. Acad. Sci. USA, 2004, 101(42), 15046-15051.
[http://dx.doi.org/10.1073/pnas.0406696101] [PMID: 15469910]
[38]
Roymans, D.; De Bondt, H.L.; Arnoult, E.; Geluykens, P.; Gevers, T.; Van Ginderen, M.; Verheyen, N.; Kim, H.; Willebrords, R.; Bonfanti, J.F.; Bruinzeel, W.; Cummings, M.D.; van Vlijmen, H.; Andries, K. Binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the RSV fusion protein. Proc. Natl. Acad. Sci. USA, 2010, 107(1), 308-313.
[http://dx.doi.org/10.1073/pnas.0910108106] [PMID: 19966279]
[39]
Takeda, M.; Leser, G.P.; Russell, C.J.; Lamb, R.A. Influenza virus hemagglutinin concentrates in lipid raft microdomains for efficient viral fusion. Proc. Natl. Acad. Sci. USA, 2003, 100(25), 14610-14617.
[http://dx.doi.org/10.1073/pnas.2235620100] [PMID: 14561897]
[40]
Rossman, J.S.; Lamb, R.A. Influenza virus assembly and budding. Virology, 2011, 411(2), 229-236.
[http://dx.doi.org/10.1016/j.virol.2010.12.003] [PMID: 21237476]
[41]
Needham, B.D.; Trent, M.S. Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis. Nat. Rev. Microbiol., 2013, 11(7), 467-481.
[http://dx.doi.org/10.1038/nrmicro3047] [PMID: 23748343]
[42]
Anaya-López, J.L.; López-Meza, J.E.; Ochoa-Zarzosa, A. Bacterial resistance to cationic antimicrobial peptides. Crit. Rev. Microbiol., 2013, 39(2), 180-195.
[http://dx.doi.org/10.3109/1040841X.2012.699025] [PMID: 22799636]
[43]
Mercer, D.K.; O’Neil, D.A. Peptides as the next generation of anti-infectives. Future Med. Chem., 2013, 5(3), 315-337.
[http://dx.doi.org/10.4155/fmc.12.213] [PMID: 23464521]
[44]
Rajendran, L.; Knölker, H.J.; Simons, K. Subcellular targeting strategies for drug design and delivery. Nat. Rev. Drug Discov., 2010, 9(1), 29-42.
[http://dx.doi.org/10.1038/nrd2897] [PMID: 20043027]
[45]
Jitendra, Sharma PK, Bansal S, Banik A. Noninvasive routes of proteins and peptides drug delivery. Indian J. Pharm. Sci., 2011, 73(4), 367-375.
[http://dx.doi.org/10.4103/0250-474X.95608]
[46]
Liderot, K.; Ahl, M.; Özenci, V. Secondary bacterial infections in patients with seasonal influenza A and pandemic H1N1. BioMed Res. Int., 2013.2013376219
[http://dx.doi.org/10.1155/2013/376219] [PMID: 23865050]
[47]
Teixeira, V.; Feio, M.J.; Bastos, M. Role of lipids in the interaction of antimicrobial peptides with membranes. Prog. Lipid Res., 2012, 51(2), 149-177.
[http://dx.doi.org/10.1016/j.plipres.2011.12.005] [PMID: 22245454]
[48]
Bian, Y.; Xie, X.S. Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications. AAPS J., 2018, 20(3), 59.
[http://dx.doi.org/10.1208/s12248-018-0216-7] [PMID: 29633051]
[49]
Kirsch, P.; Hartman, A.M.; Hirsch, A.K.H.; Empting, M. Concepts and Core Principles of Fragment-Based Drug Design. Molecules, 2019, 24(23)E4309
[http://dx.doi.org/10.3390/molecules24234309] [PMID: 31779114]
[50]
Belouzard, S.; Millet, J.K.; Licitra, B.N.; Whittaker, G.R. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses, 2012, 4(6), 1011-1033.
[http://dx.doi.org/10.3390/v4061011] [PMID: 22816037]
[51]
Li, F. Structure, Function, and Evolution of Coronavirus Spike Proteins. Annu. Rev. Virol., 2016, 3(1), 237-261.
[http://dx.doi.org/10.1146/annurev-virology-110615-042301] [PMID: 27578435]
[52]
Tang, T.; Bidon, M.; Jaimes, J.A.; Whittaker, G.R.; Daniel, S. Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antiviral Res., 2020.178104792
[http://dx.doi.org/10.1016/j.antiviral.2020.104792] [PMID: 32272173]
[53]
Bock, J.E.; Gavenonis, J.; Kritzer, J.A. Getting in shape: controlling peptide bioactivity and bioavailability using conformational constraints. ACS Chem. Biol., 2013, 8(3), 488-499.
[http://dx.doi.org/10.1021/cb300515u] [PMID: 23170954]
[54]
Rezai, T.; Bock, J.E.; Zhou, M.V.; Kalyanaraman, C.; Lokey, R.S.; Jacobson, M.P. Conformational flexibility, internal hydrogen bonding, and passive membrane permeability: successful in silico prediction of the relative permeabilities of cyclic peptides. J. Am. Chem. Soc., 2006, 128(43), 14073-14080.
[http://dx.doi.org/10.1021/ja063076p] [PMID: 17061890]
[55]
Rezai, T.; Yu, B.; Millhauser, G.L.; Jacobson, M.P.; Lokey, R.S. Testing the conformational hypothesis of passive membrane permeability using synthetic cyclic peptide diastereomers. J. Am. Chem. Soc., 2006, 128(8), 2510-2511.
[http://dx.doi.org/10.1021/ja0563455] [PMID: 16492015]
[56]
Hedlund, M.; Aschenbrenner, L.M.; Jensen, K.; Larson, J.L.; Fang, F. Sialidase-based anti-influenza virus therapy protects against secondary pneumococcal infection. J. Infect. Dis., 2010, 201(7), 1007-1015.
[http://dx.doi.org/10.1086/651170] [PMID: 20170378]
[57]
Li, C.G.; Tang, W.; Chi, X.J.; Dong, Z.M.; Wang, X.X.; Wang, X.J. A cholesterol tag at the N terminus of the relatively broad-spectrum fusion inhibitory peptide targets an earlier stage of fusion glycoprotein activation and increases the peptide’s antiviral potency in vivo. J. Virol., 2013, 87(16), 9223-9232.
[http://dx.doi.org/10.1128/JVI.01153-13] [PMID: 23804636]
[58]
Botos, I.; Wlodawer, A. Cyanovirin-N: a sugar-binding antiviral protein with a new twist. Cell. Mol. Life Sci., 2003, 60(2), 277-287.
[http://dx.doi.org/10.1007/s000180300023] [PMID: 12678493]
[59]
Kim, Y.; Lovell, S.; Tiew, K.C.; Mandadapu, S.R.; Alliston, K.R.; Battaile, K.P. Broad-spectrum antivirals against 3Cor3C-like proteases of picornaviruses, noroviruses, and coronaviruses. J. Virol., 2012, 86(21), 11754-11762.
[http://dx.doi.org/10.1128/JVI.01348-12]
[60]
Barton, C.; Kouokam, J.C.; Lasnik, A.B.; Foreman, O.; Cambon, A.; Brock, G.; Montefiori, D.C.; Vojdani, F.; McCormick, A.A.; O’Keefe, B.R.; Palmer, K.E. Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models. Antimicrob. Agents Chemother., 2014, 58(1), 120-127.
[http://dx.doi.org/10.1128/AAC.01407-13] [PMID: 24145548]
[61]
Elshabrawy, H.A.; Fan, J.; Haddad, C.S.; Ratia, K.; Broder, C.C.; Caffrey, M.; Prabhakar, B.S. Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay. J. Virol., 2014, 88(8), 4353-4365.
[http://dx.doi.org/10.1128/JVI.03050-13] [PMID: 24501399]
[62]
Blaising, J.; Polyak, S.J.; Pécheur, E.I. Arbidol as a broad-spectrum antiviral: an update. Antiviral Res., 2014, 107, 84-94.
[http://dx.doi.org/10.1016/j.antiviral.2014.04.006] [PMID: 24769245]
[63]
Diamond, M.S.; Farzan, M. The broad-spectrum antiviral functions of IFIT and IFITM proteins. Nat. Rev. Immunol., 2013, 13(1), 46-57.
[http://dx.doi.org/10.1038/nri3344] [PMID: 23237964]
[64]
Xia, S.; Lan, Q.; Pu, J.; Wang, C.; Liu, Z.; Xu, W.; Wang, Q.; Liu, H.; Jiang, S.; Lu, L. Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4. Viruses, 2019, 11(1)E56
[http://dx.doi.org/10.3390/v11010056] [PMID: 30646495]
[65]
Sainz, B., Jr; Mossel, E.C.; Gallaher, W.R.; Wimley, W.C.; Peters, C.J.; Wilson, R.B.; Garry, R.F. Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein. Virus Res., 2006, 120(1-2), 146-155.
[http://dx.doi.org/10.1016/j.virusres.2006.03.001] [PMID: 16616792]
[66]
Zhao, H.; Zhou, J.; Zhang, K.; Chu, H.; Liu, D.; Poon, V.K-M. A novel peptide withpotent and broad-spectrum antiviral activities against multiple respiratoryviruses. Sci. Rep., 2016, 6, 22008.
[67]
Gao, J.; Lu, G.; Qi, J.; Li, Y.; Wu, Y.; Deng, Y. Structure of the fusion core and inhibi-tion of fusion by a heptad repeat peptide derived from the S Protein of MiddleEast Respiratory Syndrome Coronavirus. J. Virol., 2013, 87(24), 13134-13140.
[http://dx.doi.org/10.1128/JVI.02433-13]

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