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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview

Author(s): Mehdi Oubahmane, Ismail Hdoufane, Imane Bjij, Nouhaila Ait Lahcen, Didier Villemin, Rachid Daoud, Achraf El Allali and Driss Cherqaoui*

Volume 22, Issue 21, 2022

Published on: 07 September, 2022

Page: [1776 - 1792] Pages: 17

DOI: 10.2174/1568026622666220726122339

Price: $65

Abstract

The outbreak of the SARS-CoV-2 virus in late 2019 and the spread of the COVID-19 pandemic have caused severe health and socioeconomic damage worldwide. Despite the significant research effort to develop vaccines, antiviral treatments, and repurposed therapeutics to effectively contain the catastrophe, there are no available effective vaccines or antiviral drugs that can limit the threat of the disease, so the infections continue to expand. To date, the search for effective treatment remains a global challenge. Therefore, it is imperative to develop therapeutic strategies to contain the spread of SARS-CoV-2. Like other coronaviruses, SARS-CoV-2 invades and infects human host cells via the attachment of its spike envelope glycoprotein to the human host cell receptor hACE2. Subsequently, several host cell proteases facilitate viral entry via proteolytic cleavage and activation of the S protein. These host cell proteases include type II transmembrane serine proteases (TTSPs), cysteine cathepsins B and L, furin, trypsin, and Factor Xa, among others. Given the critical role of the host cell proteases in coronavirus pathogenesis, their inhibition by small molecules has successfully targeted SARS-CoV-2 in vitro, suggesting that host cell proteases are attractive therapeutic targets for SARS-CoV-2 infection. In this review, we focus on the biochemical properties of host cell proteases that facilitate the entry of SARS-CoV-2, and we highlight therapeutic small molecule candidates that have been proposed through in silico research.

Keywords: COVID-19, SARS-CoV-2, Host cell proteases, TTSPs, Cathepsins, Furin, Small-molecule inhibitors, Proteolytic activation, and protease inhibition.

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[1]
Andersen, K.G.; Rambaut, A.; Lipkin, W.I.; Holmes, E.C.; Garry, R.F. The proximal origin of SARS-CoV-2. Nat. Med., 2020, 26(4), 450-452.
[http://dx.doi.org/10.1038/s41591-020-0820-9] [PMID: 32284615]
[2]
Chen, L.; Zhong, L. Genomics functional analysis and drug screening of SARS-CoV-2. Genes Dis., 2020, 7(4), 542-550.
[http://dx.doi.org/10.1016/j.gendis.2020.04.002] [PMID: 32363223]
[3]
Oubahmane, M.; Hdoufane, I.; Bjij, I.; Jerves, C.; Villemin, D.; Cherqaoui, D. COVID-19: In silico identification of potent α-ketoamide inhibitors targeting the main protease of the SARS-CoV-2. J. Mol. Struct., 2021, 1244, 130897.
[http://dx.doi.org/10.1016/j.molstruc.2021.130897] [PMID: 34149065]
[4]
Lan, J.; Ge, J.; Yu, J.; Shan, S.; Zhou, H.; Fan, S.; Zhang, Q.; Shi, X.; Wang, Q.; Zhang, L.; Wang, X. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 2020, 581(7807), 215-220.
[http://dx.doi.org/10.1038/s41586-020-2180-5] [PMID: 32225176]
[5]
Ou, X.; Liu, Y.; Lei, X.; Li, P.; Mi, D.; Ren, L.; Guo, L.; Guo, R.; Chen, T.; Hu, J.; Xiang, Z.; Mu, Z.; Chen, X.; Chen, J.; Hu, K.; Jin, Q.; Wang, J.; Qian, Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun., 2020, 11(1), 1620.
[http://dx.doi.org/10.1038/s41467-020-15562-9] [PMID: 32221306]
[6]
Huang, Y.; Yang, C.; Xu, X.F.; Xu, W.; Liu, S.W. Structural and functional properties of SARS-CoV-2 spike protein: Potential antivirus drug development for COVID-19. Acta Pharmacol. Sin., 2020, 41(9), 1141-1149.
[http://dx.doi.org/10.1038/s41401-020-0485-4] [PMID: 32747721]
[7]
Fehr, A.R.; Perlman, S. Coronaviruses: An overview of their replication and pathogenesis. In: Coronaviruses: Methods and Protocols;; Nature Publishing Group: Berlin, Germany, 2015; 1282, pp. 1-23.
[8]
El-Shimy, I.A.; Mohamed, M.M.A.; Hasan, S.S.; Hadi, M.A. Targeting host cell proteases as a potential treatment strategy to limit the spread of SARS-CoV-2 in the respiratory tract. Pharmacol. Res. Perspect., 2021, 9(1), e00698.
[http://dx.doi.org/10.1002/prp2.698] [PMID: 33369210]
[9]
Hwang, S.S.; Lim, J.; Yu, Z.; Kong, P.; Sefik, E.; Xu, H.; Harman, C.C.D.; Kim, L.K.; Lee, G.R.; Li, H.B.; Flavell, R.A. MRNA destabilization by BTG1 and BTG2 maintains T cell quiescence. Science (80-.), 2020, 1255-126.
[10]
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]
[11]
Zhu, C.; He, G.; Yin, Q.; Zeng, L.; Ye, X.; Shi, Y.; Xu, W. Molecular biology of the SARs-CoV-2 spike protein: A review of current knowledge. J. Med. Virol., 2021, 93(10), 5729-5741.
[http://dx.doi.org/10.1002/jmv.27132] [PMID: 34125455]
[12]
Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.; Wang, D.; Xu, W.; Wu, G.; Gao, G.F.; Tan, W. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med., 2020, 382(8), 727-733.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[13]
Hoffmann, M.; Hofmann-Winkler, H.; Pöhlmann, S. Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins. In: Activation of Viruses by Host Proteases; Springer International Publishing: Cham, 2018; pp. 71-98.
[http://dx.doi.org/10.1007/978-3-319-75474-1_4]
[14]
Gioia, M.; Ciaccio, C.; Calligari, P.; De Simone, G.; Sbardella, D.; Tundo, G.; Fasciglione, G.F.; Di Masi, A.; Di Pierro, D.; Bocedi, A.; Ascenzi, P.; Coletta, M. Role of proteolytic enzymes in the COVID-19 infection and promising therapeutic approaches. Biochem. Pharmacol., 2020, 182, 114225.
[http://dx.doi.org/10.1016/j.bcp.2020.114225] [PMID: 32956643]
[15]
Murza, A.; Dion, S.P.; Boudreault, P.L.; Désilets, A.; Leduc, R.; Marsault, É. Inhibitors of type II transmembrane serine proteases in the treatment of diseases of the respiratory tract - A review of patent literature. Expert Opin. Ther. Pat., 2020, 30(11), 807-824.
[http://dx.doi.org/10.1080/13543776.2020.1817390] [PMID: 32887532]
[16]
Shulla, A.; Heald-Sargent, T.; Subramanya, G.; Zhao, J.; Perlman, S.; Gallagher, T. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J. Virol., 2011, 85(2), 873-882.
[http://dx.doi.org/10.1128/JVI.02062-10] [PMID: 21068237]
[17]
Shin, W.J.; Seong, B.L.; Type, I.I. Type II transmembrane serine proteases as potential target for anti-influenza drug discovery. Expert Opin. Drug Discov., 2017, 12(11), 1139-1152.
[http://dx.doi.org/10.1080/17460441.2017.1372417] [PMID: 28870104]
[18]
Hedstrom, L. Serine protease mechanism and specificity. Chem. Rev., 2002, 102(12), 4501-4524.
[http://dx.doi.org/10.1021/cr000033x] [PMID: 12475199]
[19]
Bugge, T.H.; Antalis, T.M.; Wu, Q.; Type, I.I. Type II transmembrane serine proteases. J. Biol. Chem., 2009, 284(35), 23177-23181.
[http://dx.doi.org/10.1074/jbc.R109.021006] [PMID: 19487698]
[20]
Goettig, P.; Brandstetter, H.; Magdolen, V. Surface loops of trypsin-like serine proteases as determinants of function. Biochimie, 2019, 166, 52-76.
[http://dx.doi.org/10.1016/j.biochi.2019.09.004] [PMID: 31505212]
[21]
Verner, E.; Katz, B.A.; Spencer, J.R.; Allen, D.; Hataye, J.; Hruzewicz, W.; Hui, H.C.; Kolesnikov, A.; Li, Y.; Luong, C.; Martelli, A.; Radika, K.; Rai, R.; She, M.; Shrader, W.; Sprengeler, P.A.; Trapp, S.; Wang, J.; Young, W.B.; Mackman, R.L. Development of serine protease inhibitors displaying a multicentered short (<2.3 A) hydrogen bond binding mode: Inhibitors of urokinase-type plasminogen activator and factor Xa. J. Med. Chem., 2001, 44(17), 2753-2771.
[http://dx.doi.org/10.1021/jm0100638] [PMID: 11495587]
[22]
Antalis, T.M.; Bugge, T.H.; Wu, Q. Membrane-Anchored Serine Proteases in Health and Disease. In: Progress in Molecular Biology and Translational Science; Elsevier B.V., 2011; Vol. 99, pp. 1-50.
[23]
Murray, A.S.; Hyland, T.E.; Sala-Hamrick, K.E.; Mackinder, J.R.; Martin, C.E.; Tanabe, L.M.; Varela, F.A.; List, K. The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy. Oncogene, 2020, 39(41), 6421-6436.
[http://dx.doi.org/10.1038/s41388-020-01436-3] [PMID: 32868877]
[24]
Tanabe, L.M.; List, K. The role of type II transmembrane serine protease-mediated signaling in cancer. FEBS J., 2017, 284(10), 1421-1436.
[http://dx.doi.org/10.1111/febs.13971] [PMID: 27870503]
[25]
Xia, S.; Lan, Q.; Su, S.; Wang, X.; Xu, W.; Liu, Z.; Zhu, Y.; Wang, Q.; Lu, L.; Jiang, S. The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin. Signal Transduct. Target. Ther., 2020, 5(1), 92.
[http://dx.doi.org/10.1038/s41392-020-0184-0] [PMID: 32532959]
[26]
Lukassen, S.; Chua, R.L.; Trefzer, T.; Kahn, N.C.; Schneider, M.A.; Muley, T.; Winter, H.; Meister, M.; Veith, C.; Boots, A.W.; Hennig, B.P.; Kreuter, M.; Conrad, C.; Eils, R. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J., 2020, 39(10), e105114.
[http://dx.doi.org/10.15252/embj.2020105114] [PMID: 32246845]
[27]
Ziegler, C.G.K.; Allon, S.J.; Nyquist, S.K.; Mbano, I.M.; Miao, V.N.; Tzouanas, C.N.; Cao, Y.; Yousif, A.S.; Bals, J.; Hauser, B.M.; Feldman, J.; Muus, C.; Wadsworth, M.H., II; Kazer, S.W.; Hughes, T.K.; Doran, B.; Gatter, G.J.; Vukovic, M.; Taliaferro, F.; Mead, B.E.; Guo, Z.; Wang, J.P.; Gras, D.; Plaisant, M.; Ansari, M.; Angelidis, I.; Adler, H.; Sucre, J.M.S.; Taylor, C.J.; Lin, B.; Waghray, A.; Mitsialis, V.; Dwyer, D.F.; Buchheit, K.M.; Boyce, J.A.; Barrett, N.A.; Laidlaw, T.M.; Carroll, S.L.; Colonna, L.; Tkachev, V.; Peterson, C.W.; Yu, A.; Zheng, H.B.; Gideon, H.P.; Winchell, C.G.; Lin, P.L.; Bingle, C.D.; Snapper, S.B.; Kropski, J.A.; Theis, F.J.; Schiller, H.B.; Zaragosi, L.E.; Barbry, P.; Leslie, A.; Kiem, H.P.; Flynn, J.L.; Fortune, S.M.; Berger, B.; Finberg, R.W.; Kean, L.S.; Garber, M.; Schmidt, A.G.; Lingwood, D.; Shalek, A.K.; Ordovas-Montanes, J.; Banovich, N.; Brazma, A.; Desai, T.; Duong, T.E.; Eickelberg, O.; Falk, C.; Farzan, M.; Glass, I.; Haniffa, M.; Horvath, P.; Hung, D.; Kaminski, N.; Krasnow, M.; Kuhnemund, M.; Lafyatis, R.; Lee, H.; Leroy, S.; Linnarson, S.; Lundeberg, J.; Meyer, K.; Misharin, A.; Nawijn, M.; Nikolic, M.Z.; Pe’er, D.; Powell, J.; Quake, S.; Rajagopal, J.; Tata, P.R.; Rawlins, E.L.; Regev, A.; Reyfman, P.A.; Rojas, M.; Rosen, O.; Saeb-Parsy, K.; Samakovlis, C.; Schiller, H.; Schultze, J.L.; Seibold, M.A.; Shepherd, D.; Spence, J.; Spira, A.; Sun, X.; Teichmann, S.; Theis, F.; Tsankov, A.; van den Berge, M.; von Papen, M.; Whitsett, J.; Xavier, R.; Xu, Y.; Zhang, K. SARS-CoV-2 Receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell, 2020, 181(5), 1016-1035.e19.
[http://dx.doi.org/10.1016/j.cell.2020.04.035] [PMID: 32413319]
[28]
Bilinska, K.; Jakubowska, P.; Von Bartheld, C.S.; Butowt, R. Expression of the SARS-CoV-2 Entry Proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: Identification of cell types and trends with age. ACS Chem. Neurosci., 2020, 11(11), 1555-1562.
[http://dx.doi.org/10.1021/acschemneuro.0c00210] [PMID: 32379417]
[29]
Lambertz, R.L.O.; Gerhauser, I.; Nehlmeier, I.; Leist, S.R.; Kollmus, H.; Pöhlmann, S.; Schughart, K. Tmprss2 knock-out mice are resistant to H10 influenza A virus pathogenesis. J. Gen. Virol., 2019, 100(7), 1073-1078.
[http://dx.doi.org/10.1099/jgv.0.001274] [PMID: 31099738]
[30]
Iwata-Yoshikawa, N.; Okamura, T.; Shimizu, Y.; Hasegawa, H.; Takeda, M.; Nagata, N. TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. J. Virol., 2019, 93(6), 1815-1833.
[http://dx.doi.org/10.1128/JVI.01815-18] [PMID: 30626688]
[31]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2), 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[32]
Kim, T.S.; Heinlein, C.; Hackman, R.C.; Nelson, P.S. Phenotypic analysis of mice lacking the Tmprss2-encoded protease. Mol. Cell. Biol., 2006, 26(3), 965-975.
[http://dx.doi.org/10.1128/MCB.26.3.965-975.2006] [PMID: 16428450]
[33]
Deroo, B.J.; Korach, K.S. Estrogen receptors and human disease. J. Clin. Invest., 2006, 116(3), 561-570.
[http://dx.doi.org/10.1172/JCI27987] [PMID: 16511588]
[34]
Menon, M.P.; Higano, C.S. Enzalutamide, a second generation androgen receptor antagonist: Development and clinical applications in prostate cancer. Curr. Oncol. Rep., 2013, 15(2), 69-75.
[http://dx.doi.org/10.1007/s11912-013-0293-9] [PMID: 23341368]
[35]
Lecomte, S.; Demay, F.; Ferrière, F.; Pakdel, F. Phytochemicals targeting estrogen receptors: Beneficial rather than adverse effects? Int. J. Mol. Sci., 2017, 18(7), 1381.
[http://dx.doi.org/10.3390/ijms18071381] [PMID: 28657580]
[36]
Li, F.; Han, M.; Dai, P.; Xu, W.; He, J.; Tao, X.; Wu, Y.; Tong, X.; Xia, X.; Guo, W.; Zhou, Y.; Li, Y.; Zhu, Y.; Zhang, X.; Liu, Z.; Aji, R.; Cai, X.; Li, Y.; Qu, D.; Chen, Y.; Jiang, S.; Wang, Q.; Ji, H.; Xie, Y.; Sun, Y.; Lu, L.; Gao, D. Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide. Nat. Commun., 2021, 12(1), 866.
[http://dx.doi.org/10.1038/s41467-021-21171-x] [PMID: 33558541]
[37]
Almehdi, A.M.; Khoder, G.; Alchakee, A.S.; Alsayyid, A.T.; Sarg, N.H.; Soliman, S.S.M. SARS-CoV-2 spike protein: Pathogenesis, vaccines, and potential therapies. Infection, 2021, 49(5), 855-876.
[http://dx.doi.org/10.1007/s15010-021-01677-8] [PMID: 34339040]
[38]
Qiao, Y.; Wang, X.M.; Mannan, R.; Pitchiaya, S.; Zhang, Y.; Wotring, J.W.; Xiao, L.; Robinson, D.R.; Wu, Y.M.; Tien, J.C.Y.; Cao, X.; Simko, S.A.; Apel, I.J.; Bawa, P.; Kregel, S.; Narayanan, S.P.; Raskind, G.; Ellison, S.J.; Parolia, A.; Zelenka-Wang, S.; McMurry, L.; Su, F.; Wang, R.; Cheng, Y.; Delekta, A.D.; Mei, Z.; Pretto, C.D.; Wang, S.; Mehra, R.; Sexton, J.Z.; Chinnaiyan, A.M. Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2. Proc. Natl. Acad. Sci. USA, 2020, 118.
[PMID: 33310900]
[39]
Yamamoto, M.; Kiso, M.; Sakai-Tagawa, Y.; Iwatsuki-Horimoto, K.; Imai, M.; Takeda, M.; Kinoshita, N.; Ohmagari, N.; Gohda, J.; Semba, K.; Matsuda, Z.; Kawaguchi, Y.; Kawaoka, Y.; Inoue, J.I. The Anticoagulant nafamostat potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and viral infection in vitro in a cell-type-dependent manner. Viruses, 2020, 12(6), 12.
[http://dx.doi.org/10.3390/v12060629] [PMID: 32532094]
[40]
Hoffmann, M.; Schroeder, S.; Kleine-Weber, H.; Müller, M.A.; Drosten, C.; Pöhlmann, S. Nafamostat mesylate blocks activation of SARS-CoV-2: New treatment option for COVID-19. Antimicrob. Agents Chemother., 2020, 64(6), 64.
[http://dx.doi.org/10.1128/AAC.00754-20] [PMID: 32312781]
[41]
Hoffmann, M.; Hofmann-Winkler, H.; Smith, J.C.; Krüger, N.; Sørensen, L.K.; Søgaard, O.S.; Hasselstrøm, J.B.; Winkler, M.; Hempel, T.; Raich, L.; Olsson, S.; Yamazoe, T.; Yamatsuta, K.; Mizuno, H.; Ludwig, S.; Noé, F.; Sheltzer, J.M.; Kjolby, M.; Pöhlmann, S. Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity. bioRxiv, 2020, 2020, 237651.
[http://dx.doi.org/10.1101/2020.08.05.237651]
[42]
Ko, M.; Jeon, S.; Ryu, W.S.; Kim, S. Comparative analysis of antiviral efficacy of FDA-approved drugs against SARS-CoV-2 in human lung cells. J. Med. Virol., 2021, 93(3), 1403-1408.
[http://dx.doi.org/10.1002/jmv.26397] [PMID: 32767684]
[43]
Baughn, L.B.; Sharma, N.; Elhaik, E.; Sekulic, A.; Bryce, A.H.; Fonseca, R. Targeting TMPRSS2 in SARS-CoV-2 Infection. Mayo Clin. Proc., 2020, 95(9), 1989-1999.
[http://dx.doi.org/10.1016/j.mayocp.2020.06.018] [PMID: 32861340]
[44]
Kawase, M.; Shirato, K.; van der Hoek, L.; Taguchi, F.; Matsuyama, S. Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J. Virol., 2012, 86(12), 6537-6545.
[http://dx.doi.org/10.1128/JVI.00094-12] [PMID: 22496216]
[45]
Mikhaylov, E.N.; Lyubimtseva, T.A.; Vakhrushev, A.D.; Stepanov, D.; Lebedev, D.S.; Vasilieva, E.Y.; Konradi, A.O.; Shlyakhto, E.V. Bromhexine Hydrochloride Prophylaxis of COVID-19 for medical personnel: A Randomized Open-Label Study. Interdiscip. Perspect. Infect. Dis., 2022, 2022, 4693121.
[http://dx.doi.org/10.1155/2022/4693121] [PMID: 35103059]
[46]
Mahoney, M.; Damalanka, V.C.; Tartell, M.A.; Chung, D. hee; Lourenço, A.L.; Pwee, D.; Mayer Bridwell, A.E.; Hoffmann, M.; Voss, J.; Karmakar, P.; Azouz, N.P.; Klingler, A.M.; Rothlauf, P.W.; Thompson, C.E.; Lee, M.; Klampfer, L.; Stallings, C.L.; O’Donoghue, A.J.; Craik, C.S. A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells. Proc. Natl. Acad. Sci. USA, 2021, 118, e2108728118.
[http://dx.doi.org/10.1073/pnas.2108728118] [PMID: 34635581]
[47]
Hempel, T.; Raich, L.; Olsson, S.; Azouz, N.P.; Klingler, A.M.; Hoffmann, M.; Pöhlmann, S.; Rothenberg, M.E.; Noé, F. Molecular mechanism of inhibiting the SARS-CoV-2 cell entry facilitator TMPRSS2 with camostat and nafamostat. Chem. Sci. (Camb.), 2020, 12(3), 983-992.
[http://dx.doi.org/10.1039/D0SC05064D] [PMID: 35382133]
[48]
Sgrignani, J.; Cavalli, A. Computational identification of a putative allosteric binding pocket in TMPRSS2. Front. Mol. Biosci., 2021, 8, 666626.
[http://dx.doi.org/10.3389/fmolb.2021.666626] [PMID: 33996911]
[49]
Escalante, D.E.; Ferguson, D.M. Structural modeling and analysis of the SARS-CoV-2 cell entry inhibitor camostat bound to the trypsin-like protease TMPRSS2. Med. Chem. Res., 2021, 30(2), 399-409.
[http://dx.doi.org/10.1007/s00044-021-02708-7] [PMID: 33564221]
[50]
Hu, X.; Shrimp, J.H.; Guo, H.; Xu, M.; Chen, C.Z.; Zhu, W.; Zakharov, A.V.; Jain, S.; Shinn, P.; Simeonov, A.; Hall, M.D.; Shen, M. Discovery of TMPRSS2 inhibitors from virtual screening as a potential treatment of COVID-19. ACS Pharmacol. Transl. Sci., 2021, 4(3), 1124-1135.
[http://dx.doi.org/10.1021/acsptsci.0c00221] [PMID: 34136758]
[51]
Zhu, H.; Du, W.; Song, M.; Liu, Q.; Herrmann, A.; Huang, Q. Spontaneous binding of potential COVID-19 drugs (Camostat and Nafamostat) to human serine protease TMPRSS2. Comput. Struct. Biotechnol. J., 2020, 19, 467-476.
[http://dx.doi.org/10.1016/j.csbj.2020.12.035] [PMID: 33505639]
[52]
Zhao, X.; Luo, S.; Huang, K.; Xiong, D.; Zhang, J.Z.H.; Duan, L. Targeting mechanism for SARS-CoV-2 in silico: Interaction and key groups of TMPRSS2 toward four potential drugs. Nanoscale, 2021, 13(45), 19218-19237.
[http://dx.doi.org/10.1039/D1NR06313H] [PMID: 34787160]
[53]
Singh, N.; Decroly, E.; Khatib, A-M.; Villoutreix, B.O. Structure-based drug repositioning over the human TMPRSS2 protease domain: Search for chemical probes able to repress SARS-CoV-2 Spike protein cleavages. Eur. J. Pharm. Sci., 2020, 153, 105495.
[http://dx.doi.org/10.1016/j.ejps.2020.105495] [PMID: 32730844]
[54]
Oyedara, O.O.; Agbedahunsi, J.M.; Adeyemi, F.M.; Juárez-Saldivar, A.; Fadare, O.A.; Adetunji, C.O.; Rivera, G. Computational screening of phytochemicals from three medicinal plants as inhibitors of transmembrane protease serine 2 implicated in SARS-CoV-2 infection. Phytomedicine Plus, 2021, 1(4), 100135.
[http://dx.doi.org/10.1016/j.phyplu.2021.100135] [PMID: 35403085]
[55]
Jain, D.; Hossain, R.; Ahmed Khan, R.; Dey, D.; Rahman Toma, T.; Torequl Islam, M.; Janmeda, P.; Rehman Hakeem, K. Computer-aided evaluation of Anti-SARS-CoV-2 (3-Chymotrypsin-like Protease and Transmembrane Protease Serine 2 Inhibitors) activity of Cepharanthine: An in silico Approach. Biointerface Res. Appl. Chem., 2021, 12(1), 768-780.
[http://dx.doi.org/10.33263/BRIAC121.768780]
[56]
Idris, M.O.; Yekeen, A.A.; Alakanse, O.S.; Durojaye, O.A. Computer-aided screening for potential TMPRSS2 inhibitors: A combination of pharmacophore modeling, molecular docking and molecular dynamics simulation approaches. J. Biomol. Struct. Dyn., 2021, 39(15), 5638-5656.
[http://dx.doi.org/10.1080/07391102.2020.1792346] [PMID: 32672528]
[57]
Cheng, F.J.; Huynh, T.K.; Yang, C.S.; Hu, D.W.; Shen, Y.C.; Tu, C.Y.; Wu, Y.C.; Tang, C.H.; Huang, W.C.; Chen, Y.; Ho, C.Y. Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection. Nutrients, 2021, 13(8), 2800.
[http://dx.doi.org/10.3390/nu13082800] [PMID: 34444960]
[58]
Baby, K.; Maity, S.; Mehta, C.H.; Suresh, A.; Nayak, U.Y.; Nayak, Y. SARS-CoV-2 entry inhibitors by dual targeting TMPRSS2 and ACE2: An in silico drug repurposing study. Eur. J. Pharmacol., 2021, 896, 173922.
[http://dx.doi.org/10.1016/j.ejphar.2021.173922] [PMID: 33539819]
[59]
Barge, S.; Jade, D.; Gosavi, G.; Talukdar, N.C.; Borah, J. In-silico screening for identification of potential inhibitors against SARS-CoV-2 transmembrane serine protease 2 (TMPRSS2). Eur. J. Pharm. Sci., 2021, 162, 105820.
[http://dx.doi.org/10.1016/j.ejps.2021.105820] [PMID: 33775827]
[60]
Elmezayen, A.D. Al-Obaidi, A.; Şahin, A.T.; Yelekçi, K. Drug Repurposing for Coronavirus (COVID-19): In silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes. J. Biomol. Struct. Dyn., 2021, 39(8), 2980-2992.
[61]
Sarkar, N.; Thakur, A.; Ghadge, J.; Rath, S.L. Computational studies reveal Fluorine based quinolines to be potent inhibitors for proteins involved in SARS-CoV-2 assembly. J. Fluor. Chem., 2021, 250, 109865.
[http://dx.doi.org/10.1016/j.jfluchem.2021.109865] [PMID: 34393265]
[62]
Yadav, P.K.; Jaiswal, A.; Singh, R.K. In silico study on spice-derived antiviral phytochemicals against SARS-CoV-2 TMPRSS2 target. J. Biomol. Struct. Dyn., 2021. [Epub ahead of print].
[http://dx.doi.org/10.1080/07391102.2021.1965658] [PMID: 34427179]
[63]
Shree, P.; Mishra, P.; Kumar, P.; Pandey, H.; Giri, R.; Chaube, R.; Garg, N.; Tripathi, Y.B. In silico screening of Pueraria tuberosa (PTY-2) for targeting COVID-19 by countering dual targets Mpro and TMPRSS2. J. Biomol. Struct. Dyn., 2021. [Epub ahead of print].
[http://dx.doi.org/10.1080/07391102.2021.1965029] [PMID: 34424815]
[64]
Sonawane, K.D.; Barale, S.S.; Dhanavade, M.J.; Waghmare, S.R.; Nadaf, N.H.; Kamble, S.A.; Mohammed, A.A.; Makandar, A.M.; Fandilolu, P.M.; Dound, A.S.; Naik, N.M.; More, V.B. Structural insights and inhibition mechanism of TMPRSS2 by experimentally known inhibitors Camostat mesylate, Nafamostat and Bromhexine hydrochloride to control SARS-coronavirus-2: A molecular modeling approach. Inform. Med. Unlocked, 2021, 24, 100597.
[http://dx.doi.org/10.1016/j.imu.2021.100597] [PMID: 34075338]
[65]
Kishk, S.M.; Kishk, R.M.; Yassen, A.S.A.; Nafie, M.S.; Nemr, N.A.; ElMasry, G.; Al-Rejaie, S.; Simons, C. Molecular Insights into Human Transmembrane Protease Serine-2 (TMPS2) inhibitors against SARS-CoV2: Homology modelling, molecular dynamics, and docking studies. Molecules, 2020, 25(21), 5007.
[http://dx.doi.org/10.3390/molecules25215007] [PMID: 33137894]
[66]
Shakya, A.; Chikhale, R.V.; Bhat, H.R.; Alasmary, F.A.; Almutairi, T.M.; Ghosh, S.K.; Alhajri, H.M.; Alissa, S.A.; Nagar, S.; Islam, M.A. Pharmacoinformatics-based identification of transmembrane Protease Serine-2 Inhibitors from Morus alba as SARS-CoV-2 Cell Entry Inhibitors. Mol. Divers., 2021, 1, 1-14.
[PMID: 33786727]
[67]
Kashyap, D.; Jakhmola, S.; Tiwari, D.; Kumar, R.; Moorthy, N.S.H.N.; Elangovan, M.; Brás, N.F.; Jha, H.C. Plant derived active compounds as potential anti SARS-CoV-2 agents: An in-silico study. J. Biomol. Struct. Dyn., 2021. [Epub ahead of print].
[http://dx.doi.org/10.1080/07391102.2021.1947384] [PMID: 34225565]
[68]
Kaliamurthi, S.; Selvaraj, G.; Selvaraj, C.; Singh, S.K.; Wei, D-Q.; Peslherbe, G.H. Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19. Int. J. Mol. Sci., 2021, 22(13), 7071.
[http://dx.doi.org/10.3390/ijms22137071] [PMID: 34209188]
[69]
Kumar, V.; Dhanjal, J.K.; Bhargava, P.; Kaul, A.; Wang, J.; Zhang, H.; Kaul, S.C.; Wadhwa, R.; Sundar, D. Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells. J. Biomol. Struct. Dyn., 2022, 40(1), 1-13.
[http://dx.doi.org/10.1080/07391102.2020.1775704] [PMID: 32469279]
[70]
DurdaĞi, S. Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target. Turk. J. Biol., 2020, 44(3), 185-191.
[http://dx.doi.org/10.3906/biy-2005-112] [PMID: 32595355]
[71]
Ramakrishnan, J.; Kandasamy, S.; Iruthayaraj, A.; Magudeeswaran, S.; Chinnasamy, K.; Poomani, K. Strong binding of leupeptin with TMPRSS2 protease may be an alternative to camostat and nafamostat for SARS-CoV-2 repurposed drug: Evaluation from molecular docking and molecular dynamics simulations. Appl. Biochem. Biotechnol., 2021, 193(6), 1909-1923.
[http://dx.doi.org/10.1007/s12010-020-03475-8] [PMID: 33512650]
[72]
Zang, R.; Gomez Castro, M.F.; McCune, B.T.; Zeng, Q.; Rothlauf, P.W.; Sonnek, N.M.; Liu, Z.; Brulois, K.F.; Wang, X.; Greenberg, H.B.; Diamond, M.S.; Ciorba, M.A.; Whelan, S.P.J.; Ding, S. TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Sci. Immunol., 2020, 5(47), 3582.
[http://dx.doi.org/10.1126/sciimmunol.abc3582] [PMID: 32404436]
[73]
Kang, S.; Min, H.J.; Kang, M.S.; Jung, M.G.; Kim, S. Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(6), 1748-1751.
[http://dx.doi.org/10.1016/j.bmcl.2013.01.055] [PMID: 23414802]
[74]
Kim, S.; Ko, D.; Lee, Y.; Jang, S.; Lee, Y.; Lee, I.Y.; Kim, S. Anti-cancer activity of the novel 2-hydroxydiarylamide derivatives IMD-0354 and KRT1853 through suppression of cancer cell invasion, proliferation, and survival mediated by TMPRSS4. Sci. Rep., 2019, 9(1), 10003.
[http://dx.doi.org/10.1038/s41598-019-46447-7] [PMID: 31292507]
[75]
Jia, J.B.; Wang, W.Q.; Sun, H.C.; Liu, L.; Zhu, X.D.; Kong, L.Q.; Chai, Z.T.; Zhang, W.; Zhang, J.B.; Xu, H.X.; Zeng, Z.C.; Wu, W.Z.; Wang, L.; Tang, Z.Y. A novel tripeptide, tyroserleutide, inhibits irradiation-induced invasiveness and metastasis of hepatocellular carcinoma in nude mice. Invest. New Drugs, 2011, 29(5), 861-872.
[http://dx.doi.org/10.1007/s10637-010-9435-1] [PMID: 20414698]
[76]
Ilamathi, M.; Hemanth, R.; Nishanth, S.; Sivaramakrishnan, V. Identification of potential transmembrane protease serine 4 inhibitors as anti-cancer agents by integrated computational approach. J. Theor. Biol., 2016, 389, 253-262.
[http://dx.doi.org/10.1016/j.jtbi.2015.10.021] [PMID: 26590327]
[77]
Chokki, M.; Yamamura, S.; Eguchi, H.; Masegi, T.; Horiuchi, H.; Tanabe, H.; Kamimura, T.; Yasuoka, S. Human airway trypsin-like protease increases mucin gene expression in airway epithelial cells. Am. J. Respir. Cell Mol. Biol., 2004, 30(4), 470-478.
[http://dx.doi.org/10.1165/rcmb.2003-0199OC] [PMID: 14500256]
[78]
Menou, A.; Duitman, J.; Flajolet, P.; Sallenave, J.M.; Mailleux, A.A.; Crestani, B. Human airway trypsin-like protease, a serine protease involved in respiratory diseases. Am. J. Physiol. Lung Cell. Mol. Physiol., 2017, 312(5), L657-L668.
[http://dx.doi.org/10.1152/ajplung.00509.2016] [PMID: 28235951]
[79]
Yan, K.; Hu, C.; Liu, C.; Chu, G.; Wang, X.; Ma, S.; Li, L. Retracted Article: Knockdown of TMPRSS11D inhibits the proliferation, migration and invasion of cervical cancer cells. RSC Advances, 2019, 9(37), 21591-21600.
[http://dx.doi.org/10.1039/C9RA02482D] [PMID: 35521321]
[80]
Tharappel, A.M.; Samrat, S.K.; Li, Z.; Li, H. Targeting Crucial Host Factors of SARS-CoV-2. ACS Infect. Dis., 2020, 6(11), 2844-2865.
[http://dx.doi.org/10.1021/acsinfecdis.0c00456] [PMID: 33112126]
[81]
Sielaff, F.; Böttcher-Friebertshäuser, E.; Meyer, D.; Saupe, S.M.; Volk, I.M.; Garten, W.; Steinmetzer, T. Development of substrate analogue inhibitors for the human airway trypsin-like protease HAT. Bioorg. Med. Chem. Lett., 2011, 21(16), 4860-4864.
[http://dx.doi.org/10.1016/j.bmcl.2011.06.033] [PMID: 21741839]
[82]
Dalton, J.P.; Neill, S.O.; Stack, C.; Collins, P.; Walshe, A.; Sekiya, M.; Doyle, S.; Mulcahy, G.; Hoyle, D.; Khaznadji, E.; Moiré, N.; Brennan, G.; Mousley, A.; Kreshchenko, N.; Maule, A.G.; Donnelly, S.M. Fasciola hepatica cathepsin L-like proteases: Biology, function, and potential in the development of first generation liver fluke vaccines. Int. J. Parasitol., 2003, 33(11), 1173-1181.
[http://dx.doi.org/10.1016/S0020-7519(03)00171-1] [PMID: 13678633]
[83]
Carrilho, M.R.; Scaffa, P.; Oliveira, V.; Tjäderhane, L.; Tersariol, I.L.; Pashley, D.H.; Tay, F.; Nascimento, F.D. Insights into cathepsin-B activity in mature dentin matrix. Arch. Oral Biol., 2020, 117, 104830.
[http://dx.doi.org/10.1016/j.archoralbio.2020.104830] [PMID: 32673819]
[84]
Dvoryakova, E.A.; Vinokurov, K.S.; Tereshchenkova, V.F.; Dunaevsky, Y.E.; Belozersky, M.A.; Oppert, B.; Filippova, I.Y.; Elpidina, E.N. Primary digestive cathepsins L of Tribolium castaneum larvae: Proteomic identification, properties, comparison with human Lysosomal cathepsin L. Insect Biochem. Mol. Biol., 2022, 140, 103679.
[http://dx.doi.org/10.1016/j.ibmb.2021.103679] [PMID: 34763092]
[85]
Drobny, A.; Prieto Huarcaya, S.; Dobert, J.; Kluge, A.; Bunk, J.; Schlothauer, T.; Zunke, F. The role of lysosomal cathepsins in neurodegeneration: Mechanistic insights, diagnostic potential and therapeutic approaches. Biochim. Biophys. Acta Mol. Cell Res., 2022, 1869(7), 119243.
[http://dx.doi.org/10.1016/j.bbamcr.2022.119243] [PMID: 35217144]
[86]
Di Spiezio, A.; Marques, A.R.A.; Schmidt, L.; Thießen, N.; Gallwitz, L.; Fogh, J.; Bartsch, U.; Saftig, P. Analysis of cathepsin B and cathepsin L treatment to clear toxic lysosomal protein aggregates in neuronal ceroid lipofuscinosis. Biochim. Biophys. Acta Mol. Basis Dis., 2021, 1867(10), 166205.
[http://dx.doi.org/10.1016/j.bbadis.2021.166205] [PMID: 34214607]
[87]
Liu, T.; Luo, S.; Libby, P.; Shi, G.P. Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients. Pharmacol. Ther., 2020, 213, 107587.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107587] [PMID: 32470470]
[88]
Pišlar, A. Mitrović A.; Sabotič J.; Pečar Fonović U.; Perišić Nanut, M.; Jakoš, T.; Senjor, E.; Kos, J. The role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors. PLoS Pathog., 2020, 16(11), e1009013.
[http://dx.doi.org/10.1371/journal.ppat.1009013] [PMID: 33137165]
[89]
Kim, W.; Kang, K. Recent developments of cathepsin inhibitors and their selectivity. Expert Opin. Ther. Pat., 2002, 12(3), 419-432.
[http://dx.doi.org/10.1517/13543776.12.3.419]
[90]
Dana, D.; Pathak, S.K. A review of small molecule inhibitors and functional probes of human cathepsin L. Molecules, 2020, 25(3), 698.
[91]
Brix, K. Host Cell Proteases: Cathepsins. In: Activation of Viruses by Host Proteases; Springer International Publishing: Cham, 2018; pp. 249-276.
[http://dx.doi.org/10.1007/978-3-319-75474-1_10]
[92]
Saudenova, M.; Promnitz, J.; Ohrenschall, G.; Himmerkus, N.; Böttner, M.; Kunke, M.; Bleich, M.; Theilig, F. Behind every smile there’s teeth: Cathepsin B’s function in health and disease with a kidney view. Biochim. Biophys. Acta, 2022, 1869(4), 119190.
[93]
Lalmanach, G.; Saidi, A.; Bigot, P.; Chazeirat, T.; Lecaille, F.; Wartenberg, M. Regulation of the proteolytic activity of cysteine cathepsins by oxidants. Int. J. Mol. Sci., 2020, 21(6), 21.
[http://dx.doi.org/10.3390/ijms21061944] [PMID: 32178437]
[94]
Coulombe, R.; Grochulski, P.; Sivaraman, J.; Ménard, R.; Mort, J.S.; Cygler, M. Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment. EMBO J., 1996, 15(20), 5492-5503.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb00934.x] [PMID: 8896443]
[95]
Verma, S.; Dixit, R.; Pandey, K.C. Cysteine proteases: Modes of activation and future prospects as pharmacological targets. Front. Pharmacol., 2016, 7, 107.
[http://dx.doi.org/10.3389/fphar.2016.00107] [PMID: 27199750]
[96]
Li, Y.Y.; Fang, J.; Ao, G.Z. Cathepsin B and L inhibitors: A patent review (2010 - present). Expert Opin. Ther. Pat., 2017, 27(6), 643-656.
[http://dx.doi.org/10.1080/13543776.2017.1272572] [PMID: 27998201]
[97]
Rawlings, N.D.; Barrett, A.J.; Finn, R. Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res., 2016, 44(D1), D343-D350.
[http://dx.doi.org/10.1093/nar/gkv1118] [PMID: 26527717]
[98]
Patel, S.; Homaei, A.; El-Seedi, H.R.; Akhtar, N. Cathepsins: Proteases that are vital for survival but can also be fatal. Biomed. Pharmacother., 2018, 105, 526-532.
[http://dx.doi.org/10.1016/j.biopha.2018.05.148] [PMID: 29885636]
[99]
Raghav, N.; Garg, S. N-formylpyrazolines and N-benzoylpyra-zolines as novel inhibitors of mammalian cathepsin B and cathepsin H. Bioorg. Chem., 2014, 57, 43-50.
[http://dx.doi.org/10.1016/j.bioorg.2014.07.012] [PMID: 25181676]
[100]
Buckle, D.R.; Rockell, C.J.M.; Smith, H.; Spicer, B.A. Studies on 1,2,3-triazoles. 13. (Piperazinylalkoxy) [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-ones with combined H1-antihistamine and mast cell stabilizing properties. J. Med. Chem., 1986, 29(11), 2262-2267.
[http://dx.doi.org/10.1021/jm00161a022] [PMID: 2431143]
[101]
Cianni, L.; Rocho, F.D.R.; Bonatto, V.; Martins, F.C.P.; Lameira, J.; Leitão, A.; Montanari, C.A.; Shamim, A. Design, synthesis and stepwise optimization of nitrile-based inhibitors of cathepsins B and L. Bioorg. Med. Chem., 2021, 29, 115827.
[http://dx.doi.org/10.1016/j.bmc.2020.115827] [PMID: 33254069]
[102]
Sharma, K.; Raghav, N. Curcumin analogs as anti-cathepsins agents: Designing, virtual screening, and molecular docking analysis. Comput. Toxicol., 2021, 19, 100174.
[http://dx.doi.org/10.1016/j.comtox.2021.100174]
[103]
Madadlou, A. Food proteins are a potential resource for mining cathepsin L inhibitory drugs to combat SARS-CoV-2. Eur. J. Pharmacol., 2020, 885, 173499.
[http://dx.doi.org/10.1016/j.ejphar.2020.173499] [PMID: 32841639]
[104]
Saroha, B.; Kumar, G.; Kumar, S.; Kumari, M.; Rani, M.; Raghav, N.; Sahoo, P.K.; Ghosh, S.; Mahata, S.; Nasare, V.D. Ultrasound assisted a one pot multicomponent and greener synthesis of 1,2,3-triazole incorporated aurone hybrids: Cathepsin b inhibition, anti-cancer activity against ags cell line, and in-silico docking evaluation. Curr. Res. Green Sustain. Chem., 2022, 19(8), 100295.
[105]
Raghav, N.; Jangra, S.; Kumar, A.; Bhattacharyya, S. Quinazoline derivatives as cathepsins B, H and L inhibitors and cell proliferating agents. Int. J. Biol. Macromol., 2017, 94(Pt A), 719-727.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.10.001] [PMID: 27780761]
[106]
Gurung, A.B. In silico structure modelling of SARS-CoV-2 Nsp13 helicase and Nsp14 and repurposing of FDA approved antiviral drugs as dual inhibitors. Gene Rep., 2020, 21, 100860.
[http://dx.doi.org/10.1016/j.genrep.2020.100860] [PMID: 32875166]
[107]
Pandey, V.; Sharma, K.; Raghav, N. Ligand-Based Modeling of Semicarbazones and Thiosemicarbazones Derivatives as Cathepsin B, H, and L Inhibitors: A Multi-Target Approach. J. Mol. Struct., 2022, 1257, 132612.
[http://dx.doi.org/10.1016/j.molstruc.2022.132612]
[108]
Wang, Q.; Qiu, Y.; Li, J.Y.; Zhou, Z.J.; Liao, C.H.; Ge, X.Y. A Unique protease cleavage site predicted in the spike protein of the novel pneumonia coronavirus (2019-nCoV) potentially related to viral transmissibility. Virol. Sin., 2020, 35(3), 337-339.
[http://dx.doi.org/10.1007/s12250-020-00212-7] [PMID: 32198713]
[109]
Ortutay, Z.; Grönholm, A.; Laitinen, M.; Keresztes-Andrei, M.; Hermelo, I.; Pesu, M. Identification of Novel Genetic Regulatory Region for Proprotein Convertase FURIN and Interferon Gamma in T Cells. Front. Immunol., 2021, 12, 630389.
[http://dx.doi.org/10.3389/fimmu.2021.630389] [PMID: 33679774]
[110]
Izaguirre, G. The proteolytic regulation of virus cell entry by furin and other proprotein convertases. Viruses, 2019, 11(9), 837.
[http://dx.doi.org/10.3390/v11090837] [PMID: 31505793]
[111]
Örd, M.; Faustova, I.; Loog, M. The sequence at Spike S1/S2 site enables cleavage by furin and phospho-regulation in SARS-CoV2 but not in SARS-CoV1 or MERS-CoV. Sci. Rep., 2020, 10(1), 16944.
[http://dx.doi.org/10.1038/s41598-020-74101-0] [PMID: 33037310]
[112]
Whittaker, G.R. SARS-CoV-2 spike and its adaptable furin cleavage site. Lancet Microbe, 2021, 2(10), e488-e489.
[http://dx.doi.org/10.1016/S2666-5247(21)00174-9] [PMID: 34396356]
[113]
Zhang, Y.; Zhang, L.; Wu, J.; Yu, Y.; Liu, S.; Li, T.; Li, Q.; Ding, R.; Wang, H.; Nie, J.; Cui, Z.; Wang, Y.; Huang, W.; Wang, Y. A second functional furin site in the SARS-CoV-2 spike protein. Emerg. Microbes Infect., 2022, 11(1), 182-194.
[http://dx.doi.org/10.1080/22221751.2021.2014284] [PMID: 34856891]
[114]
Coutard, B.; Valle, C.; de Lamballerie, X.; Canard, B.; Seidah, N.G.; Decroly, E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res., 2020, 176, 104742.
[http://dx.doi.org/10.1016/j.antiviral.2020.104742] [PMID: 32057769]
[115]
Lodermeyer, V.; Suhr, K.; Schrott, N.; Kolbe, C.; Stürzel, C.M.; Krnavek, D.; Münch, J.; Dietz, C.; Waldmann, T.; Kirchhoff, F.; Goffinet, C. 90K, an interferon-stimulated gene product, reduces the infectivity of HIV-1. Retrovirology, 2013, 10(1), 111.
[http://dx.doi.org/10.1186/1742-4690-10-111] [PMID: 24156545]
[116]
Braun, E.; Sauter, D. Furin-mediated protein processing in infectious diseases and cancer. Clin. Transl. Immunology, 2019, 8(8), e1073.
[http://dx.doi.org/10.1002/cti2.1073] [PMID: 31406574]
[117]
Tang, T.; Jaimes, J.A.; Bidon, M.K.; Straus, M.R.; Daniel, S.; Whittaker, G.R. Proteolytic Activation of SARS-CoV-2 Spike at the S1/S2 Boundary: Potential Role of Proteases beyond Furin. ACS Infect. Dis., 2021, 7(2), 264-272.
[http://dx.doi.org/10.1021/acsinfecdis.0c00701] [PMID: 33432808]
[118]
Jean, F.; Stella, K.; Thomas, L.; Liu, G.; Xiang, Y.; Reason, A.J.; Thomas, G. alpha1-antitrypsin Portland, a bioengineered serpin highly selective for furin: Application as an antipathogenic agent. Proc. Natl. Acad. Sci. USA, 1998, 95(13), 7293-7298.
[http://dx.doi.org/10.1073/pnas.95.13.7293] [PMID: 9636142]
[119]
Tanikawa, T.; Hayashi, T.; Suzuki, R.; Kitamura, M.; Inoue, Y. Inhibitory Effect of Honokiol on Furin-like Activity and SARS-CoV-2 Infection. J. Tradit. Complement. Med., 2022, 12(1), 69-72.
[PMID: 34545325]
[120]
Cheng, Y.W.; Chao, T.L.; Li, C.L.; Chiu, M.F.; Kao, H.C.; Wang, S.H.; Pang, Y.H.; Lin, C.H.; Tsai, Y.M.; Lee, W.H.; Tao, M.H.; Ho, T.C.; Wu, P.Y.; Jang, L.T.; Chen, P.J.; Chang, S.Y.; Yeh, S.H. Furin inhibitors block SARS-CoV-2 spike protein cleavage to suppress virus production and cytopathic effects. Cell Rep., 2020, 33(2), 108254.
[http://dx.doi.org/10.1016/j.celrep.2020.108254] [PMID: 33007239]
[121]
Mitra, P. Inhibiting fusion with cellular membrane system: Therapeutic options to prevent severe acute respiratory syndrome coronavirus-2 infection. Am. J. Physiol. Cell Physiol., 2020, 319(3), C500-C509.
[http://dx.doi.org/10.1152/ajpcell.00260.2020] [PMID: 32687406]
[122]
Mao, B.; Le-Trilling, V.T.K.; Wang, K.; Mennerich, D.; Hu, J.; Zhao, Z.; Zheng, J.; Deng, Y.; Katschinski, B.; Xu, S.; Zhang, G.; Cai, X.; Hu, Y.; Wang, J.; Lu, M.; Huang, A.; Tang, N.; Trilling, M.; Lin, Y. Obatoclax inhibits SARS-CoV-2 entry by altered endosomal acidification and impaired cathepsin and furin activity in vitro. Emerg. Microbes Infect., 2022, 11(1), 483-497.
[http://dx.doi.org/10.1080/22221751.2022.2026739] [PMID: 34989664]
[123]
Dahal, A.; Sonju, J.J.; Kousoulas, K.G.; Jois, S.D. Peptides and peptidomimetics as therapeutic agents for Covid-19. Pept. Sci. (Hoboken), 2021, 114, e24245.
[PMID: 34901700]
[124]
Havranek, B.; Islam, S.M. An in silico approach for identification of novel inhibitors as potential therapeutics targeting COVID-19 main protease. J. Biomol. Struct. Dyn., 2021, 39(12), 4304-4315.
[http://dx.doi.org/10.1080/07391102.2020.1776158] [PMID: 32544024]
[125]
Negahdaripour, M.; Rahbar, M.R.; Mosalanejad, Z.; Gholami, A. Theta-Defensins to Counter COVID-19 as Furin Inhibitors: In silico efficiency prediction and novel compound design. Comput. Math. Methods Med., 2022, 2022, 9735626.
[http://dx.doi.org/10.1155/2022/9735626] [PMID: 35154362]
[126]
Vardhan, S.; Sahoo, S.K. Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells. J. Tradit. Complement. Med., 2022, 12(1), 6-15.
[http://dx.doi.org/10.1016/j.jtcme.2021.04.001] [PMID: 33868970]
[127]
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]
[128]
Jaimes, J.A.; Millet, J.K.; Whittaker, G.R. Proteolytic cleavage of the SARS-CoV-2 Spike protein and the role of the novel S1/S2 Site. iScience, 2020, 23(6), 101212.
[http://dx.doi.org/10.1016/j.isci.2020.101212] [PMID: 32512386]
[129]
Mustafa, Z.; Zhanapiya, A.; Kalbacher, H.; Burster, T. Neutrophil elastase and proteinase 3 cleavage sites are adjacent to the polybasic sequence within the proteolytic sensitive activation loop of the SARS-CoV-2 spike protein. ACS Omega, 2021, 6(10), 7181-7185.
[http://dx.doi.org/10.1021/acsomega.1c00363] [PMID: 33748632]
[130]
Hoffmann, M.; Kleine-Weber, H.; Pöhlmann, S. A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol. Cell, 2020, 78(4), 779-784.e5.
[http://dx.doi.org/10.1016/j.molcel.2020.04.022] [PMID: 32362314]
[131]
Jaimes, J.A.; André, N.M.; Chappie, J.S.; Millet, J.K.; Whittaker, G.R. Phylogenetic analysis and structural modeling of SARS-CoV-2 spike protein reveals an evolutionary distinct and proteolytically sensitive activation loop. J. Mol. Biol., 2020, 432(10), 3309-3325.
[http://dx.doi.org/10.1016/j.jmb.2020.04.009] [PMID: 32320687]
[132]
Zhou, J.; Li, C.; Chen, A.; Zhu, J.; Zou, M.; Liao, H.; Yu, Y. Structural and functional relationship of Cassia obtusifolia trypsin inhibitor to understand its digestive resistance against Pieris rapae. Int. J. Biol. Macromol., 2020, 148, 908-920.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.01.193] [PMID: 31981663]
[133]
de Medeiros, A.F.; de Souza, B.B.P.; Coutinho, L.P.; Murad, A.M.; Dos Santos, P.I.M.; Monteiro, N.K.V.; Santos, E.A.D.; Maciel, B.L.L.; de Araújo Morais, A.H. Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L. J. Enzyme Inhib. Med. Chem., 2021, 36(1), 480-490.
[http://dx.doi.org/10.1080/14756366.2021.1876686] [PMID: 33491503]
[134]
Wang, Y.Q.; Zhang, H.M.; Kang, Y.J.; Gu, Y.L.; Cao, J. Mechanism of curcumin-induced trypsin inhibition: Computational and experimental studies. J. Mol. Struct., 2016, 1107, 91-98.
[http://dx.doi.org/10.1016/j.molstruc.2015.11.026]
[135]
Momeni, L.; Shareghi, B.; Farhadian, S.; Vaziri, S.; Saboury, A.A.; Raisi, F. A molecular simulation and spectroscopic approach to the binding affinity between trypsin and 2-propanol and protein conformation. Int. J. Biol. Macromol., 2018, 119, 477-485.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.07.162] [PMID: 30059735]
[136]
Momeni, L.; Farhadian, S.; Shareghi, B. Study on the interaction of ethylene glycol with trypsin: Binding ability, activity, and stability. J. Mol. Liq., 2022, 350, 118542.
[http://dx.doi.org/10.1016/j.molliq.2022.118542]
[137]
Martinez-Gonzalez, A.I.; Díaz-Sánchez, Á.G.; De la Rosa, L.A.; Bustos-Jaimes, I.; Alvarez-Parrilla, E. A novel approach to trypsin inhibition by flavonoids. J. Food Bioact., 2021, 14, 102-113.
[http://dx.doi.org/10.31665/JFB.2021.14272]
[138]
Esmon, C.T. Targeting factor Xa and thrombin: Impact on coagulation and beyond. Thromb. Haemost., 2014, 111(4), 625-633.
[http://dx.doi.org/10.1160/TH13-09-0730] [PMID: 24336942]
[139]
Jackson, C.M. Structure and function of factor X: Properties, activation, and activity in prothrombinase. A retrospective in a historical context. J. Thromb. Thrombolysis, 2021, 52(2), 371-378.
[http://dx.doi.org/10.1007/s11239-021-02421-7] [PMID: 33725285]
[140]
Maag, A.; van Rein, N.; Schuijt, T.J.; Kopatz, W.F.; Kruijswijk, D.; Thomassen, S.; Hackeng, T.M.; Camire, R.M.; van der Poll, T.; Meijers, J.C.M.; Bos, M.H.A.; van ’t Veer, C. Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa. J. Thromb. Haemost., 2022, 20(2), 328-338.
[http://dx.doi.org/10.1111/jth.15589] [PMID: 34773381]
[141]
Böttcher-Friebertshäuser, E.; Garten, W.; Klenk, H.D. Activation of viruses by host proteases; Springer, 2018.
[http://dx.doi.org/10.1007/978-3-319-75474-1]

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