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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Perspective

Interfering with the Reactive Cysteine Proteome in COVID-19

Author(s): Marcos Martinez-Banaclocha*

Volume 29, Issue 10, 2022

Published on: 23 June, 2021

Page: [1657 - 1663] Pages: 7

DOI: 10.2174/0929867328666210623142811

Abstract

Although vaccination against SARS-CoV-2 infection has been initiated, effective therapies for severe COVID-19 disease are still needed. A promising therapeutic strategy is using FDA-approved drugs that have the biological potential to interfere with or modify some of the viral proteins capable of changing the disease's course. Recent studies highlight that some clinically safe drugs can suppress the viral life cycle while potentially promoting an adequate host inflammatory/immune response by interfering with the disease's cysteine proteome.

Keywords: Cysteine, redox, proteome, ebselen, N-acetyl-cysteine, Covid-19, immunity.

« Previous Next »
[1]
Fenouillet, E.; Barbouche, R.; Jones, I.M. Cell entry by enveloped viruses: Redox considerations for HIV and SARS-coronavirus. Antioxid. Redox Signal., 2007, 9(8), 1009-1034.
[http://dx.doi.org/10.1089/ars.2007.1639] [PMID: 17567241]
[2]
Amin, S.A.; Banerjee, S.; Gayen, S.; Jha, T. Protease targeted COVID-19 drug discovery: What we have learned from the past SARS-CoV inhibitors? Eur. J. Med. Chem., 2021, 215, 113294.
[http://dx.doi.org/10.1016/j.ejmech.2021.113294] [PMID: 33618158 ]
[3]
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]
[4]
McKee, D.L.; Sternberg, A.; Stange, U.; Laufer, S.; Naujokat, C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol. Res., 2020, 157, 104859.
[http://dx.doi.org/10.1016/j.phrs.2020.104859] [PMID: 32360480]
[5]
Tsuji, M. Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease. FEBS Open Bio, 2020, 10(6), 995-1004.
[http://dx.doi.org/10.1002/2211-5463.12875] [PMID: 32374074]
[6]
Mengist, H.M.; Dilnessa, T.; Jin, T. Structural basis of potential inhibitors targeting SARS-CoV-2 Main protease. Front Chem., 2021, 9, 622898.
[http://dx.doi.org/10.3389/fchem.2021.622898] [PMID: 33889562]
[7]
Santos, I.A.; Grosche, V.R.; Bergamini, F.R.G.; Sabino-Silva, R.; Jardim, A.C.G. Antivirals against coronaviruses: Candidate drugs for SARS-CoV-2 treatment? Front. Microbiol., 2020, 11, 1818.
[http://dx.doi.org/10.3389/fmicb.2020.01818] [PMID: 32903349]
[8]
Wang, Q.; Zhang, Y.; Wu, L.; Niu, S.; Song, C.; Zhang, Z.; Lu, G.; Qiao, C.; Hu, Y.; Yuen, K.Y.; Wang, Q.; Zhou, H.; Yan, J.; Qi, J. Structural and functional basis of sars-cov-2 entry by using human ACE2. Cell, 2020, 181(4), 894-904.e9.
[http://dx.doi.org/10.1016/j.cell.2020.03.045] [PMID: 32275855]
[9]
Singh, J.; Dhindsa, R.S.; Misra, V.; Singh, B. SARS-CoV2 infectivity is potentially modulated by host redox status. Comput. Struct. Biotechnol. J., 2020, 18, 3705-3711.
[http://dx.doi.org/10.1016/j.csbj.2020.11.016] [PMID: 33250972]
[10]
Lopez, L.A.; Riffle, A.J.; Pike, S.L.; Gardner, D.; Hogue, B.G. Importance of conserved cysteine residues in the coronavirus envelope protein. J. Virol., 2008, 82(6), 3000-3010.
[http://dx.doi.org/10.1128/JVI.01914-07] [PMID: 18184703]
[11]
Boscarino, J.A.; Logan, H.L.; Lacny, J.J.; Gallagher, T.M. Envelope protein palmitoylations are crucial for murine coronavirus assembly. J. Virol., 2008, 82(6), 2989-2999.
[http://dx.doi.org/10.1128/JVI.01906-07] [PMID: 18184706]
[12]
Schoeman, D.; Fielding, B.C. Is there a link between the pathogenic human coronavirus envelope protein and immunopathology? A review of the literature. Front. Microbiol., 2020, 11, 2086.
[http://dx.doi.org/10.3389/fmicb.2020.02086] [PMID: 33013759]
[13]
Zhang, L.; Lin, D.; Sun, X.; Curth, U.; Drosten, C.; Sauerhering, L.; Becker, S.; Rox, K.; Hilgenfeld, R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 2020, 368(6489), 409-412.
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
[14]
Báez-Santos, Y.M.; St John, S.E.; Mesecar, A.D. The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds. Antiviral Res., 2015, 115, 21-38.
[http://dx.doi.org/10.1016/j.antiviral.2014.12.015] [PMID: 25554382]
[15]
Osipiuk, J.; Azizi, S.A.; Dvorkin, S.; Endres, M.; Jedrzejczak, R.; Jones, K.A.; Kang, S.; Kathayat, R.S.; Kim, Y.; Lisnyak, V.G.; Maki, S.L.; Nicolaescu, V.; Taylor, C.A.; Tesar, C.; Zhang, Y.A.; Zhou, Z.; Randall, G.; Michalska, K.; Snyder, S.A.; Dickinson, B.C.; Joachimiak, A. Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors. Nat. Commun., 2021, 12(1), 743.
[http://dx.doi.org/10.1038/s41467-021-21060-3] [PMID: 33531496]
[16]
Sargsyan, K.; Lin, C-C.; Chen, T.; Grauffel, C.; Chen, Y-P.; Yang, W-Z.; Yuan, H.S.; Lim, C. Multi-targeting of functional cysteines in multiple conserved SARS-CoV-2 domains by clinically safe Zn-ejectors. Chem. Sci. (Camb.), 2020, 11, 9904-9909.
[http://dx.doi.org/10.1039/D0SC02646H]
[17]
Jin, Z.; Du, X.; Xu, Y.; Deng, Y.; Liu, M.; Zhao, Y.; Zhang, B.; Li, X.; Zhang, L.; Peng, C.; Duan, Y.; Yu, J.; Wang, L.; Yang, K.; Liu, F.; Jiang, R.; Yang, X.; You, T.; Liu, X.; Yang, X.; Bai, F.; Liu, H.; Liu, X.; Guddat, L.W.; Xu, W.; Xiao, G.; Qin, C.; Shi, Z.; Jiang, H.; Rao, Z.; Yang, H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature, 2020, 582(7811), 289-293.
[http://dx.doi.org/10.1038/s41586-020-2223-y] [PMID: 32272481]
[18]
Debnath, U.; Mitra, A.; Dewaker, V.; Prabhakar, Y.S.; Tadala, R.; Krishnan, K.; Wagh, P.; Velusamy, U.; Subramani, C.; Agarwal, S.; Vrati, S.; Baliyan, A.; Kurpad, A.V.; Bhattacharyya, P.; Mandal, A. N-acetylcysteine: A tool to perturb SARS-CoV-2 spike protein conformation. ChemRxiv 2020.
[http://dx.doi.org/10.26434/chemrxiv.12687923.v2]
[19]
Morse, J.S.; Lalonde, T.; Xu, S.; Liu, W.R. Learning from the past: Possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019- nCoV. Chem Bio Chem,, 2020, 21(5), 730-738.
[http://dx.doi.org/10.1002/cbic.202000047] [PMID: 32022370]
[20]
Ghahremanpour, M.M.; Tirado-Rives, J.; Deshmukh, M.; Ippolito, J.A.; Zhang, C.H.; Cabeza de Vaca, I.; Liosi, M.E.; Anderson, K.S.; Jorgensen, W.L. Identification of 14 known drugs as inhibitors of the Main protease of SARS-CoV-2. ACS Med. Chem. Lett., 2020, 11(12), 2526-2533.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00521] [PMID: 33324471]
[21]
Dai, W.; Zhang, B.; Jiang, X.M.; Su, H.; Li, J.; Zhao, Y.; Xie, X.; Jin, Z.; Peng, J.; Liu, F.; Li, C.; Li, Y.; Bai, F.; Wang, H.; Cheng, X.; Cen, X.; Hu, S.; Yang, X.; Wang, J.; Liu, X.; Xiao, G.; Jiang, H.; Rao, Z.; Zhang, L.K.; Xu, Y.; Yang, H.; Liu, H. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science, 2020, 368(6497), 1331-1335.
[http://dx.doi.org/10.1126/science.abb4489] [PMID: 32321856]
[22]
Qin, B.; Craven, G.B.; Hou, P.; Lu, X.; Child, E.S.; Morgan, R.M.L.; Armstrong, A.; Mann, D.J.; Cui, S. Acrylamide fragment inhibitors that induce unprecedented conformational distortions in enterovirus 71 3C and SARS-CoV-2 Main protease. bioRxiv, 2020.
[23]
Hoffman, R.L.; Kania, R.S.; Brothers, M.A.; Davies, J.F.; Ferre, R.A.; Gajiwala, K.S.; He, M.; Hogan, R.J.; Kozminski, K.; Li, L.Y.; Lockner, J.W.; Lou, J.; Marra, M.T.; Mitchell, L.J., Jr; Murray, B.W.; Nieman, J.A.; Noell, S.; Planken, S.P.; Rowe, T.; Ryan, K.; Smith, G.J., III; Solowiej, J.E.; Steppan, C.M.; Taggart, B. Discovery of ketone-based covalent inhibitors of coronavirus 3cl proteases for the potential therapeutic treatment of covid-19. J. Med. Chem., 2020, 63(21), 12725-12747.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01063] [PMID: 33054210]
[24]
Lobo-Galo, N.; Terrazas-López, M.; Martínez-Martínez, A.; Díaz-Sánchez, Á.G. FDA-approved thiol-reacting drugs that potentially bind into the SARS-CoV-2 main protease, essential for viral replication. J. Biomol. Struct. Dyn., 2021, 39(9), 3419-3427.
[http://dx.doi.org/10.1080/07391102.2020.1764393] [PMID: 32364011]
[25]
Khanna, K.; Raymond, W.; Charbit, A.R.; Jin, J.; Gitlin, I.; Tang, M.; Sperber, H.S.; Franz, S.; Pillai, S.; Simmons, G.; Fahy, J.V. Binding of SARS-CoV-2 spike protein to ACE2 is disabled by thiol-based drugs; evidence from in vitro SARS-CoV-2 infection studies. bioRxiv, 2020.
[26]
Hati, S.; Bhattacharyya, S. Impact of thiol-disulfide balance on the binding of Covid-19 spike protein with angiotensin-converting enzyme 2 receptor. ACS Omega, 2020, 5(26), 16292-16298.
[http://dx.doi.org/10.1021/acsomega.0c02125] [PMID: 32656452]
[27]
Shin, D.; Mukherjee, R.; Grewe, D.; Bojkova, D.; Baek, K.; Bhattacharya, A.; Schulz, L.; Widera, M.; Mehdipour, A.R.; Tascher, G.; Geurink, P.P.; Wilhelm, A.; van der Heden van Noort, G.J.; Ovaa, H.; Müller, S.; Knobeloch, K.P.; Rajalingam, K.; Schulman, B.A.; Cinatl, J.; Hummer, G.; Ciesek, S.; Dikic, I. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature, 2020, 587(7835), 657-662.
[http://dx.doi.org/10.1038/s41586-020-2601-5] [PMID: 32726803]
[28]
Bade, V.N.; Nickels, J.; Keusekotten, K.; Praefcke, G.J. Covalent protein modification with ISG15 via a conserved cysteine in the hinge region. PLoS One, 2012, 7(6), e38294.
[http://dx.doi.org/10.1371/journal.pone.0038294] [PMID: 22693631]
[29]
Prinarakis, E.; Chantzoura, E.; Thanos, D.; Spyrou, G. S-glutathionylation of IRF3 regulates IRF3-CBP interaction and activation of the IFN beta pathway. EMBO J., 2008, 27(6), 865-875.
[http://dx.doi.org/10.1038/emboj.2008.28] [PMID: 18309294]
[30]
Mullen, L.; Mengozzi, M.; Hanschmann, E.M.; Alberts, B.; Ghezzi, P. How the redox state regulates immunity. Free Radic. Biol. Med., 2020, 157, 3-14.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.12.022] [PMID: 31899344]
[31]
García-Piñeres, A.J.; Castro, V.; Mora, G.; Schmidt, T.J.; Strunck, E.; Pahl, H.L.; Merfort, I. Cysteine 38 in p65/NF-kappaB plays a crucial role in DNA binding inhibition by sesquiterpene lactones. J. Biol. Chem., 2001, 276(43), 39713-39720.
[http://dx.doi.org/10.1074/jbc.M101985200] [PMID: 11500489]
[32]
Matthews, J.R.; Wakasugi, N.; Virelizier, J.L.; Yodoi, J.; Hay, R.T. Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62. Nucleic Acids Res., 1992, 20(15), 3821-3830.
[http://dx.doi.org/10.1093/nar/20.15.3821] [PMID: 1508666]
[33]
Gilmore, T.D.; Herscovitch, M. Inhibitors of NF-kappaB signaling: 785 and counting. Oncogene, 2006, 25(51), 6887-6899.
[http://dx.doi.org/10.1038/sj.onc.1209982] [PMID: 17072334]
[34]
Yin, Z.; Machius, M.; Nestler, E.J.; Rudenko, G. Activator protein-1: Redox switch controlling structure and DNA-binding. Nucleic Acids Res., 2017, 45(19), 11425-11436.
[http://dx.doi.org/10.1093/nar/gkx795] [PMID: 28981703]
[35]
Del Sorbo, L.; Zhang, H. Is there a place for N-acetylcysteine in the treatment of septic shock? Crit. Care, 2004, 8(2), 93-95.
[http://dx.doi.org/10.1186/cc2450] [PMID: 15025765]
[36]
Sekhar, R.V.; Patel, S.G.; Guthikonda, A.P.; Reid, M.; Balasubramanyam, A.; Taffet, G.E.; Jahoor, F. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am. J. Clin. Nutr., 2011, 94(3), 847-853.
[http://dx.doi.org/10.3945/ajcn.110.003483] [PMID: 21795440]
[37]
Martinez-Banaclocha, M. Cellular cysteine network (Cysteinet): Pharmacological intervention in brain aging and neurodegenerative diseases.Frontiers in clinical drug researchcentral nervous system; Atta, Ur-Rahman, Ed.; Bentham Science Publishers, , 2016; 2, pp. 105-172.
[38]
De Flora, S.; Balansky, R.; La Maestra, S. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J., 2020, 34(10), 13185-13193.
[http://dx.doi.org/10.1096/fj.202001807] [PMID: 32780893]

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