Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Compounds based on Adamantyl-substituted Amino Acids and Peptides as Potential Antiviral Drugs Acting as Viroporin Inhibitors

Author(s): Timur M. Garaev, Tatyana V. Grebennikova, Varvara V. Lebedeva, Varvara V. Avdeeva* and Viktor F. Larichev

Volume 30, Issue 12, 2024

Published on: 12 March, 2024

Page: [912 - 920] Pages: 9

DOI: 10.2174/0113816128286111240229074810

Price: $65

Abstract

The discussion has revolved around the derivatives of amino acids and peptides containing carbocycles and their potential antiviral activity in vitro against influenza A, hepatitis C viruses, and coronavirus. Studies conducted on cell cultures reveal that aminoadamantane amino acid derivatives exhibit the capacity to hinder the replication of viruses containing viroporins. Furthermore, certain compounds demonstrate potent virucidal activity with respect to influenza A/H5N1 and hepatitis C virus particles. A conceptual framework for viroporin inhibitors has been introduced, incorporating carbocyclic motifs as membranotropic carriers in the structure, alongside a functional segment comprised of amino acids and peptides. These components correspond to the interaction with the inner surface of the channel's pore or another target protein.

[1]
Adamson CS, Chibale K, Goss RJM, Jaspars M, Newman DJ, Dorrington RA. Antiviral drug discovery: Preparing for the next pandemic. Chem Soc Rev 2021; 50(6): 3647-55.
[http://dx.doi.org/10.1039/D0CS01118E] [PMID: 33524090]
[2]
Chew MF, Poh KS, Poh CL. Peptides as therapeutic agents for dengue virus. Int J Med Sci 2017; 14(13): 1342-59.
[http://dx.doi.org/10.7150/ijms.21875] [PMID: 29200948]
[3]
Wanka L, Iqbal K, Schreiner PR. The lipophilic bullet hits the targets: Medicinal chemistry of adamantane derivatives. Chem Rev 2013; 113(5): 3516-604.
[http://dx.doi.org/10.1021/cr100264t] [PMID: 23432396]
[4]
Shibnev VA, Deryabin PG, Garaev TM, Finogenova MP, Botikov AG, Mishin DV. Peptide carbocyclic derivatives as inhibitors of the viroporin function of RNA-containing viruses. Russ J Bioorganic Chem 2017; 43(5): 517-25.
[http://dx.doi.org/10.1134/S1068162017050132]
[5]
Avdeeva VV, Garaev TM, Malinina EA, Zhizhin KY, Kuznetsov NT. Physiologically active compounds based on membranotropic cage carriers–derivatives of adamantane and polyhedral boron clusters (Review). Russ J Inorg Chem 2022; 67(1): 28-47.
[http://dx.doi.org/10.1134/S0036023622010028]
[6]
Nieva JL, Madan V, Carrasco L. Viroporins: Structure and biological functions. Nat Rev Microbiol 2012; 10(8): 563-74.
[http://dx.doi.org/10.1038/nrmicro2820] [PMID: 22751485]
[7]
Breitinger U, Farag NS, Sticht H, Breitinger HG. Viroporins: Structure, function, and their role in the life cycle of SARS-CoV-2. Int J Biochem Cell Biol 2022; 145: 106185.
[http://dx.doi.org/10.1016/j.biocel.2022.106185] [PMID: 35219876]
[8]
Xia X, Cheng A, Wang M, et al. Functions of viroporins in the viral life cycle and their regulation of host cell responses. Front Immunol 2022; 13: 890549.
[http://dx.doi.org/10.3389/fimmu.2022.890549] [PMID: 35720341]
[9]
Li Y, Surya W, Claudine S, Torres J. Structure of a conserved Golgi complex-targeting signal in coronavirus envelope proteins. J Biol Chem 2014; 289(18): 12535-49.
[http://dx.doi.org/10.1074/jbc.M114.560094] [PMID: 24668816]
[10]
Li Y, To J, Verdià-Baguena C, et al. Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment. J Virol 2014; 88(20): 11899-914.
[http://dx.doi.org/10.1128/JVI.00839-14] [PMID: 25100835]
[11]
Hsu HJ, Lin MH, Schindler C, Fischer WB. Structure based computational assessment of channel properties of assembled ORF-8a from SARS-CoV. Proteins 2015; 83(2): 300-8.
[http://dx.doi.org/10.1002/prot.24721] [PMID: 25394339]
[12]
Hoenen T, Groseth A. Virus–host cell interactions. Cells 2022; 11(5): 804.
[http://dx.doi.org/10.3390/cells11050804] [PMID: 35269425]
[13]
Payne S. Virus interactions with the cell. Viruses 2017; 23-35.
[http://dx.doi.org/10.1016/B978-0-12-803109-4.00003-9]
[14]
Hoenen T, Groseth A, Eds. Virus-Host Cell Interactions. Cells. MDPI Books 2023.
[http://dx.doi.org/10.3390/books978-3-0365-6558-3]
[15]
Tran L, Choi SB, Al-Najjar BO, Yusuf M, Wahab HA, Le L. Discovery of potential M2 channel inhibitors based on the amantadine scaffold via virtual screening and pharmacophore modeling. Molecules 2011; 16(12): 10227-55.
[http://dx.doi.org/10.3390/molecules161210227] [PMID: 22158591]
[16]
Musharrafieh R, Ma C, Wang J. Discovery of M2 channel blockers targeting the drug-resistant double mutants M2-S31N/L26I and M2-S31N/V27A from the influenza A viruses. Eur J Pharm Sci 2020; 141: 105124.
[http://dx.doi.org/10.1016/j.ejps.2019.105124] [PMID: 31669761]
[17]
Shen Z, Lou K, Wang W. New small-molecule drug design strategies for fighting resistant influenza A. Acta Pharm Sin B 2015; 5(5): 419-30.
[http://dx.doi.org/10.1016/j.apsb.2015.07.006] [PMID: 26579472]
[18]
Miao Y, Fu R, Zhou HX, Cross TA. Dynamic short hydrogen bonds in histidine tetrad of full-length M2 proton channel reveal tetrameric structural heterogeneity and functional mechanism. Structure 2015; 23(12): 2300-8.
[http://dx.doi.org/10.1016/j.str.2015.09.011] [PMID: 26526851]
[19]
Wei C, Pohorille A. M2 proton channel: Toward a model of a primitive proton pump. Orig Life Evol Biosph 2015; 45(1-2): 241-8.
[http://dx.doi.org/10.1007/s11084-015-9421-x] [PMID: 25777465]
[20]
Lin C, Lindenbach BD, Prágai BM, McCourt DW, Rice CM. Processing in the hepatitis C virus E2-NS2 region: Identification of p7 and two distinct E2-specific products with different C termini. J Virol 1994; 68(8): 5063-73.
[http://dx.doi.org/10.1128/jvi.68.8.5063-5073.1994] [PMID: 7518529]
[21]
Griffin S, Clarke D, McCormick C, Rowlands D, Harris M. Signal peptide cleavage and internal targeting signals direct the hepatitis C virus p7 protein to distinct intracellular membranes. J Virol 2005; 79(24): 15525-36.
[http://dx.doi.org/10.1128/JVI.79.24.15525-15536.2005] [PMID: 16306623]
[22]
Griffin SDC, Harvey R, Clarke DS, Barclay WS, Harris M, Rowlands DJ. A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. J Gen Virol 2004; 85(2): 451-61.
[http://dx.doi.org/10.1099/vir.0.19634-0] [PMID: 14769903]
[23]
Shibnev VA, Garaev TM, Finogenova MP, et al. New adamantane derivatives capable of overcoming the resistance of influenza A (H1N1) pdm2009 and A (H3N2) for “rimantadine”. Bull Exp Biol Med 2012; 153(2): 233-5.
[http://dx.doi.org/10.1007/s10517-012-1684-x] [PMID: 22816091]
[24]
Chuang GY, Kozakov D, Brenke R, Beglov D, Guarnieri F, Vajda S. Binding hot spots and amantadine orientation in the influenza a virus M2 proton channel. Biophys J 2009; 97(10): 2846-53.
[http://dx.doi.org/10.1016/j.bpj.2009.09.004] [PMID: 19917240]
[25]
Garaev TM, Odnovorov AI, Lashkov AA, et al. Studying the effect of amino acid substitutions in the M2 Ion channel of the influenza virus on the antiviral activity of the aminoadamantane derivative in vitro and in silico. Adv Pharm Bull 2020; 11(4): 700-11.
[http://dx.doi.org/10.34172/apb.2021.079] [PMID: 34888217]
[26]
Haviernik J, Štefánik M, Fojtíková M, et al. Arbidol (Umifenovir): A broad-spectrum antiviral drug that inhibits medically important arthropod-borne flaviviruses. Viruses 2018; 10(4): 184.
[http://dx.doi.org/10.3390/v10040184] [PMID: 29642580]
[27]
Shibnev VA, Garaev TM, Finogenova MP, Shevchenko ES, Burtseva EI. New adamantane derivatives can overcome resistance of influenza A(H1N1)pdm2009 and A(H3N2) viruses to remantadine. Bull Exp Biol Med 2012; 153(2): 233-5.
[http://dx.doi.org/10.1007/s10517-012-1684-x] [PMID: 22816091]
[28]
Deryabin PG, Garaev TM, Finogenova MP, Odnovorov AI. Assessment of the antiviral activity of 2HCl*H-His-Rim compound compared to the anti-influenza drug Arbidol for influenza caused by A/duck/Novosibirsk/56/05 (H5N1) (Influenza A virus, Alphainfluenzavirus, Orthomyxoviridae). Probl Virol 2019; 64(6): 268-73.
[http://dx.doi.org/10.36233/0507-4088-2019-64-6-268-273] [PMID: 32168440]
[29]
Garaev TM, Odnovorov AI, Kirillova ES, et al. Adamantan derivatives capable of inhibiting the reproduction of a Rimantadine resistant strain of influenza A(H1N1)pdm09 virus (Influenza A virus, Alphainfluenzavirus, Orthomyxoviridae). Probl Virol 2020; 65(1): 16-20.
[http://dx.doi.org/10.36233/0507-4088-2020-65-1-16-20] [PMID: 32496716]
[30]
Shibnev VA, Garaev TM, Deryabin PG, Finogenova MP, Mishin DV. Synthesis and antiviral activity of adamantylpeptides against hepatitis C virus. Pharm Chem J 2015; 49(7): 449-54.
[http://dx.doi.org/10.1007/s11094-015-1302-0]
[31]
Foster TL, Verow M, Wozniak AL, et al. Resistance mutations define specific antiviral effects for inhibitors of the hepatitis C virus p7 ion channel. Hepatology 2011; 54(1): 79-90.
[http://dx.doi.org/10.1002/hep.24371] [PMID: 21520195]
[32]
Deryabin PG, Lvov DK. A highly productive variant of the hepatitis C virus. Isolation, characterization, identification. Doklady 1998; 358(5): 688-91.
[33]
Griffin SDC, Beales LP, Clarke DS, et al. The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine. FEBS Lett 2003; 535(1-3): 34-8.
[http://dx.doi.org/10.1016/S0014-5793(02)03851-6] [PMID: 12560074]
[34]
Bildziukevich U, Özdemir Z, Wimmer Z. Recent achievements in medicinal and supramolecular chemistry of betulinic acid and its derivatives ‡. Molecules 2019; 24(19): 3546.
[http://dx.doi.org/10.3390/molecules24193546] [PMID: 31574991]
[35]
Grzywacz D, Liberek B, Myszka H. Synthesis, modification and biological activity of diosgenyl β-d-glycosaminosides: An overview. Molecules 2020; 25(22): 5433.
[http://dx.doi.org/10.3390/molecules25225433] [PMID: 33233558]
[36]
Somsák L, Ed. Carbohydrate-spiro-heterocycles. Springer International Publishing 2019.
[http://dx.doi.org/10.1007/978-3-030-31942-7]
[37]
Hu W, Zeng S, Li C, Jie Y, Li Z, Chen L. Identification of hits as matrix-2 protein inhibitors through the focused screening of a small primary amine library. J Med Chem 2010; 53(9): 3831-4.
[http://dx.doi.org/10.1021/jm901664a] [PMID: 20394375]
[38]
Wang J, Ma C, Balannik V, Pinto LH, Lamb RA, DeGrado WF. Exploring the requirements for the hydrophobic scaffold and polar amine in inhibitors of m2 from influenza a virus. ACS Med Chem Lett 2011; 2(4): 307-12.
[http://dx.doi.org/10.1021/ml100297w] [PMID: 21691418]
[39]
Avdeeva VV, Garaev TM, Breslav NV, et al. New type of RNA virus replication inhibitor based on decahydro-closo-decaborate anion containing amino acid ester pendant group. Eur J Biochem 2022; 27(4-5): 421-9.
[http://dx.doi.org/10.1007/s00775-022-01937-4] [PMID: 35332377]
[40]
Garaev TM, Grebennikova TV, Avdeeva VV, Lebedeva VV, Larichev VF. Antiviral properties of synthetic histidine derivatives containing membranotropic volumetrical carbocycles in their molecule against SARS-CoV-2 virus in vitro. Probl Virol 2023; 68(1): 18-25.
[http://dx.doi.org/10.36233/0507-4088-147] [PMID: 36961232]
[41]
Saftić D, Studzińska M, Paradowska E, et al. Comparative study of the effects of ortho-, meta- and para-carboranes (C2B10H12) on the physicochemical properties, cytotoxicity and antiviral activity of uridine and 2′-deoxyuridine boron cluster conjugates. Bioorg Chem 2020; 94: 103466.
[http://dx.doi.org/10.1016/j.bioorg.2019.103466] [PMID: 31826808]
[42]
Białek-Pietras M, Olejniczak AB, Paradowska E, et al. Synthesis and in vitro antiviral activity of lipophilic pyrimidine nucleoside/carborane conjugates. J Organomet Chem 2015; 798: 99-105.
[http://dx.doi.org/10.1016/j.jorganchem.2015.07.002]
[43]
Garaev TM, Grebennikova TV, Avdeeva VV, Malinina EA, Kuznetsov NT, Zhizhin KYu. Amino acid derivative of decahydrocloso-decaborate anion and its antiviral activity against influenza A virus. RU Patent 2749006C1, 2020.
[44]
Shibnev VA, Deryabin PG, Burtseva EI, Garaev TM, Finogenova MP, Kirillova ES. Amino acid derivatives of 2-norbornanoacetic acid and their anti-influenza activity. RU Patent 2676699C1, 2018.
[45]
Avdeeva VV, Malinina EA, Kuznetsov NT. Boron cluster anions and their derivatives in complexation reactions. Coord Chem Rev 2022; 469: 214636.
[http://dx.doi.org/10.1016/j.ccr.2022.214636]
[46]
Sivaev IB, Bregadze VI, Sjöberg S. Chemistry of closo-Dodecaborate Anion [B12H12]2-: A review. Collect Czech Chem Commun 2002; 67(6): 679-727.
[http://dx.doi.org/10.1135/cccc20020679]
[47]
Sivaev IB, Prikaznov AV, Naoufal D. Fifty years of the closo-decaborate anion chemistry. Collect Czech Chem Commun 2010; 75(11): 1149-99.
[http://dx.doi.org/10.1135/cccc2010054]
[48]
Kaniowski D, Ebenryter-Olbinska K, Kulik K, et al. Boron clusters as a platform for new materials: composites of nucleic acids and oligofunctionalized carboranes (C2B10H12) and their assembly into functional nanoparticles. Nanoscale 2020; 12(1): 103-14.
[http://dx.doi.org/10.1039/C9NR06550D] [PMID: 31763634]
[49]
Pazderová L, Tüzün EZ, Bavol D, Litecká M, Fojt L, Grűner B. Chemistry of carbon-substituted derivatives of cobalt bis(dicarbollide)(1−) ion and recent progress in boron substitution. Molecules 2023; 28(19): 6971.
[http://dx.doi.org/10.3390/molecules28196971] [PMID: 37836814]
[50]
Scholz M, Hey-Hawkins E. Carbaboranes as pharmacophores: Properties, synthesis, and application strategies. Chem Rev 2011; 111(11): 7035-62.
[http://dx.doi.org/10.1021/cr200038x] [PMID: 21780840]
[51]
Ďorďovič V, Tošner Z, Uchman M, et al. Stealth amphiphiles: Self-assembly of polyhedral boron clusters. Langmuir 2016; 32(26): 6713-22.
[http://dx.doi.org/10.1021/acs.langmuir.6b01995] [PMID: 27287067]
[52]
King RB. Three-dimensional aromaticity in polyhedral boranes and related molecules. Chem Rev 2001; 101(5): 1119-52.
[http://dx.doi.org/10.1021/cr000442t] [PMID: 11710215]
[53]
Chen Z, King RB. Spherical aromaticity: Recent work on fullerenes, polyhedral boranes, and related structures. Chem Rev 2005; 105(10): 3613-42.
[http://dx.doi.org/10.1021/cr0300892] [PMID: 16218562]
[54]
Lesnikowski ZJ. Boron units as pharmacophores - new applications and opportunities of boron cluster chemistry. Collect Czech Chem Commun 2007; 72(12): 1646-58.
[http://dx.doi.org/10.1135/cccc20071646]
[55]
Zhao X, Yang Z, Chen H, Wang Z, Zhou X, Zhang H. Progress in three-dimensional aromatic-like closo-dodecaborate. Coord Chem Rev 2021; 444: 214042.
[http://dx.doi.org/10.1016/j.ccr.2021.214042]
[56]
Hey-Hawkins E, Viñas Teixidor C, Eds. Boron-Based Compounds: Potential and Emerging Applications in Medicine. John Wiley & Sons Ltd. 2018.
[http://dx.doi.org/10.1002/9781119275602]
[57]
Fink K, Uchman M. Boron cluster compounds as new chemical leads for antimicrobial therapy. Coord Chem Rev 2021; 431: 213684.
[http://dx.doi.org/10.1016/j.ccr.2020.213684]
[58]
Matveev EY, Garaev TM, Novikov SS, et al. Derivatives of the closo-decaborate anion with pendant functional groups as inhibitors of viral replication. Russ J Inorg Chem 2023; 68(6): 670-7.
[http://dx.doi.org/10.1134/S0036023623600533]
[59]
Martin DA, Redshaw S. Amino acid derivatives and their acidadditive salts. RF Patent RU 2071470C1,
[60]
Tahir ul Qamar M, Alqahtani SM, Alamri MA, Chen LL. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. J Pharm Anal 2020; 10(4): 313-9.
[http://dx.doi.org/10.1016/j.jpha.2020.03.009] [PMID: 32296570]
[61]
Dai W, Zhang B, Jiang XM, et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science 2020; 368(6497): 1331-5.
[http://dx.doi.org/10.1126/science.abb4489] [PMID: 32321856]
[62]
Shibnev VA, Deryabin PG, Burtseva EI, Garaev TM, Finogenova MP, Kirillova ES. Derivatives of 2-quinaldinecarboxylic acid and their antiviral activity. RU Patent 2624906C1, 2017.
[63]
Cao Y, Yang R, Lee I, et al. Characterization of the SARS-CoV-2 E protein: Sequence, structure, viroporin, and inhibitors. Protein Sci 2021; 30(6): 1114-30.
[http://dx.doi.org/10.1002/pro.4075] [PMID: 33813796]
[64]
Abreu AGE, Aguilar HME, Covarrubias HD, Durán RF. Amantadine as a drug to mitigate the effects of COVID-19. Med Hypotheses 2020; 140: 109755.
[http://dx.doi.org/10.1016/j.mehy.2020.109755] [PMID: 32361100]
[65]
Vuong W, Khan MB, Fischer C, et al. Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nat Commun 2020; 11(1): 4282.
[http://dx.doi.org/10.1038/s41467-020-18096-2] [PMID: 32855413]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy