Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage.
Covid-19
Potato
Protease inhibitor
Tissue preteolysis
Viral infection
Journal
Journal of molecular medicine (Berlin, Germany)
ISSN: 1432-1440
Titre abrégé: J Mol Med (Berl)
Pays: Germany
ID NLM: 9504370
Informations de publication
Date de publication:
21 Feb 2024
21 Feb 2024
Historique:
received:
17
01
2024
accepted:
22
01
2024
revised:
17
01
2024
medline:
21
2
2024
pubmed:
21
2
2024
entrez:
21
2
2024
Statut:
aheadofprint
Résumé
Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix. Here, we assess the potential of protease inhibitors (PI) derived from potatoes in inhibiting viral infection and reducing tissue damage. The original full spectrum of potato PI was developed into five fractions by means of chromatography and hydrolysis. Individual fractions showed varying inhibitory efficacy towards a panel of proteases including trypsin, chymotrypsin, ACE2, elastase, and cathepsins B and L. The fractions did not interfere with SARS-CoV-2 infection of Vero E6 cells in vitro. Importantly, two of the fractions fully inhibited elastin-degrading activity of complete primary human neutrophil degranulate. These data warrant further development of potato PI fractions for biomedical purposes, including tissue damage crucial to SARS-CoV-2 pathogenesis. KEY MESSAGES: Protease inhibitor fractions from potato differentially inhibit a series of human proteases involved in viral replication and in tissue damage by overshoot inflammation. Protease inhibition of cell surface receptors such as ACE2 does not prevent virus infection of Vero cells in vitro. Protease inhibitors derived from potato can fully inhibit elastin-degrading primary human neutrophil proteases. Protease inhibitor fractions can be produced at high scale (hundreds of thousands of kilograms, i.e., tons) allowing economically feasible application in lower and higher income countries.
Identifiants
pubmed: 38381158
doi: 10.1007/s00109-024-02423-x
pii: 10.1007/s00109-024-02423-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Kohl NE, Emini EA, Schleif WA, Davis LJ, Heimbach JC, Dixon R, Scolnick EM, Sigal IS (1988) Active human immunodeficiency virus protease is required for viral infectivity. Proceedings of the National Academy of Sciences of USA 85:4686–4690. https://doi.org/10.1073/pnas.85.13.4686
doi: 10.1073/pnas.85.13.4686
Kräusslich H-G, Wimmer E (1988) Viral proteinases. Annu Rev Biochem 57:701–754. https://doi.org/10.1146/annurev.bi.57.070188.003413
doi: 10.1146/annurev.bi.57.070188.003413
pubmed: 3052288
Nowak T, Färber PM, Wengler G, Wengler G (1989) Analyses of the terminal sequences of west nile virus structural proteins and of the in vitro translation of these proteins allow the proposal of a complete scheme of the proteolytic cleavages involved in their synthesis. Virology 169:365–376. https://doi.org/10.1016/0042-6822(89)90162-1
doi: 10.1016/0042-6822(89)90162-1
pubmed: 2705302
Sharma A, Gupta SP (2017) Chapter 1 — Fundamentals of viruses and their proteases. In: Gupta SP (ed) In Viral proteases and their inhibitors. (Academic Press), pp 1–24. https://doi.org/10.1016/B978-0-12-809712-0.00001-0
doi: 10.1016/B978-0-12-809712-0.00001-0
Bazan JF, Fletterick RJ (1989) Detection of a trypsin-like serine protease domain in flaviviruses and pestviruses. Virology 171:637–639. https://doi.org/10.1016/0042-6822(89)90639-9
doi: 10.1016/0042-6822(89)90639-9
pubmed: 2548336
Ding J, McGrath W, Mangel W, Sweet R (1996) Crystal structure of the human adenovirus protease with its 11 amino-acid cofactor at 1.6 Å resolution. Acta Crystallogr A 52:C167–C167. https://doi.org/10.1107/S0108767396092598
doi: 10.1107/S0108767396092598
Patel S (2017) A critical review on serine protease: Key immune manipulator and pathology mediator. Allergol Immunopathol 45:579–591. https://doi.org/10.1016/j.aller.2016.10.011
doi: 10.1016/j.aller.2016.10.011
Spinelli S, Liu QZ, Alzari PM, Hirel PH, Poljak RJ (1991) The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. Biochimie 73:1391–1396. https://doi.org/10.1016/0300-9084(91)90169-2
doi: 10.1016/0300-9084(91)90169-2
pubmed: 1799632
Verma S, Dixit R, Pandey KC (2016) Cysteine proteases: modes of activation and future prospects as pharmacological targets. Front Pharmacol 7. https://doi.org/10.3389/fphar.2016.00107
Klenk H-D, Rott R, Orlich M, Blödorn J (1975) Activation of influenza A viruses by trypsin treatment. Virology 68:426–439. https://doi.org/10.1016/0042-6822(75)90284-6
doi: 10.1016/0042-6822(75)90284-6
pubmed: 173078
Tang T, Bidon M, Jaimes JA, Whittaker GR, Daniel S (2020) Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antiviral Res 178:104792. https://doi.org/10.1016/j.antiviral.2020.104792
doi: 10.1016/j.antiviral.2020.104792
pubmed: 32272173
pmcid: 7194977
Jackson CB, Farzan M, Chen B, Choe H (2022) Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 23:3–20. https://doi.org/10.1038/s41580-021-00418-x
doi: 10.1038/s41580-021-00418-x
pubmed: 34611326
Peacock TP, Goldhill DH, Zhou J, Baillon L, Frise R, Swann OC, Kugathasan R, Penn R, Brown JC, Sanchez-David RY et al (2021) The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat Microbiol 6:899–909. https://doi.org/10.1038/s41564-021-00908-w
doi: 10.1038/s41564-021-00908-w
pubmed: 33907312
Hou Y, Yu T, Wang T, Ding Y, Cui Y, Nie H (2022) Competitive cleavage of SARS-CoV-2 spike protein and epithelial sodium channel by plasmin as a potential mechanism for COVID-19 infection. American Journal of Physiology-Lung Cellular and Molecular Physiology 323:L569–L577. https://doi.org/10.1152/ajplung.00152.2022
doi: 10.1152/ajplung.00152.2022
pubmed: 36193902
pmcid: 9639761
Kim Y, Jang G, Lee D, Kim N, Seon JW, Kim Y-H, Lee C (2022) Trypsin enhances SARS-CoV-2 infection by facilitating viral entry. Adv Virol 167:441–458. https://doi.org/10.1007/s00705-021-05343-0
doi: 10.1007/s00705-021-05343-0
Schurink B, Roos E, Radonic T, Barbe E, Bouman CSC, de Boer HH, de Bree GJ, Bulle EB, Aronica EM, Florquin S et al (2020) Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. The Lancet Microbe 1:e290–e299. https://doi.org/10.1016/S2666-5247(20)30144-0
doi: 10.1016/S2666-5247(20)30144-0
pubmed: 33015653
pmcid: 7518879
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X et al (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 395:497–506. https://doi.org/10.1016/S0140-6736(20)30183-5
doi: 10.1016/S0140-6736(20)30183-5
Belouzard S, Madu I, Whittaker GR (2010) Elastase-mediated activation of the severe acute respiratory syndrome coronavirus spike protein at discrete Sites within the S2 domain. J Biol Chem 285:22758–22763. https://doi.org/10.1074/jbc.M110.103275
doi: 10.1074/jbc.M110.103275
pubmed: 20507992
pmcid: 2906266
Wang J, Li Q, Yin Y, Zhang Y, Cao Y, Lin X, Huang L, Hoffmann D, Lu M, Qiu Y (2020) Excessive neutrophils and neutrophil extracellular traps in COVID-19. Front Immunol 11:2063. https://doi.org/10.3389/fimmu.2020.02063
doi: 10.3389/fimmu.2020.02063
pubmed: 33013872
pmcid: 7461898
Pouvreau L, Gruppen H, Piersma SR, van den Broek LAM, van Koningsveld GA, Voragen AGJ (2001) Relative abundance and inhibitory distribution of protease inhibitors in potato juice from cv. Elkana. J Agric Food Chem 49:2864–2874. https://doi.org/10.1021/jf010126v
doi: 10.1021/jf010126v
pubmed: 11409980
Kowalczewski PŁ, Olejnik A, Świtek S, Bzducha-Wróbel A, Kubiak P, Kujawska M, Lewandowicz G (2022) Bioactive compounds of potato (Solanum tuberosum L.) juice: from industry waste to food and medical applications. Crit Rev Plant Sci 41:52–89. https://doi.org/10.1080/07352689.2022.2057749
doi: 10.1080/07352689.2022.2057749
Ruseler-van Embden JGH, Van Lieshout LMC, Smits SA, Van Kessel I, Laman JD (2004) Potato tuber proteins efficiently inhibit human faecal proteolytic activity: implications for treatment of peri-anal dermatitis. Eur J Clin Invest 34:303–311. https://doi.org/10.1111/j.1365-2362.2004.01330.x
doi: 10.1111/j.1365-2362.2004.01330.x
pubmed: 15086363
FDA (2013) GRN No. 447 Potato protein isolates. https://www.cfsanappsexternal.fda.gov/scripts/fdcc/?set=GRASNotices&id=447&sort=GRN_No&order=DESC&startrow=1&type=basic&search=447
Pouvreau LAM (2004) Occurrence and physico-chemical properties of protease inhibitors from potato tuber (Solanum tuberosum). PhD thesis. Wageningen university. https://edepot.wur.nl/35450
ter Ellen BM, Dinesh Kumar N, Bouma EM, Troost B, van de Pol DPI, van der Ende-Metselaar HH, Apperloo L, van Gosliga D, van den Berge M, Nawijn MC et al (2021) Resveratrol and pterostilbene inhibit SARS-CoV-2 replication in air–liquid interface cultured human primary bronchial epithelial cells. Viruses 13:1335
doi: 10.3390/v13071335
pubmed: 34372541
pmcid: 8309965
Chua RL, Lukassen S, Trump S, Hennig BP, Wendisch D, Pott F, Debnath O, Thürmann L, Kurth F, Völker MT et al (2020) COVID-19 severity correlates with airway epithelium–immune cell interactions identified by single-cell analysis. Nat Biotechnol 38:970–979. https://doi.org/10.1038/s41587-020-0602-4
doi: 10.1038/s41587-020-0602-4
pubmed: 32591762
Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I, Nagata N, Sekizuka T, Katoh H, Kato F et al (2020) Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci 117:7001–7003. https://doi.org/10.1073/pnas.2002589117
doi: 10.1073/pnas.2002589117
pubmed: 32165541
pmcid: 7132130
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N-H, Nitsche A et al (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:271-280.e278. https://doi.org/10.1016/j.cell.2020.02.052
doi: 10.1016/j.cell.2020.02.052
pubmed: 32142651
pmcid: 7102627
Koch J, Uckeley ZM, Doldan P, Stanifer M, Boulant S, Lozach P-Y (2021) TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells. EMBO J 40:e107821
doi: 10.15252/embj.2021107821
pubmed: 34159616
pmcid: 8365257
Wettstein L, Weil T, Conzelmann C, Müller JA, Groß R, Hirschenberger M, Seidel A, Klute S, Zech F, Prelli Bozzo C et al (2021) Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection. Nat Commun 12:1726. https://doi.org/10.1038/s41467-021-21972-0
doi: 10.1038/s41467-021-21972-0
pubmed: 33741941
pmcid: 7979852
Brzin J, Popović T, Drobnic-Kosorok M, Kotnik M, Turk V (1998) Inhibitors of cysteine proteinases from potato. Bio Chem Hoppe-Seyler 369:233–238
Valueva TA, Revina TA, Kladnitskaya GV, Mosolov VV, Mentele P (1999) Primary structure of a 21-kD protein from potato tubers. Biochemistry Biokhimiia 64:1258–1265
pubmed: 10611530
Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J et al (2020) Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 11:1620. https://doi.org/10.1038/s41467-020-15562-9
doi: 10.1038/s41467-020-15562-9
pubmed: 32221306
pmcid: 7100515
Zhao M-M, Yang W-L, Yang F-Y, Zhang L, Huang W-J, Hou W, Fan C-F, Jin R-H, Feng Y-M, Wang Y-C, Yang J-K (2021) Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development. Signal Transduct Target Ther 6:134. https://doi.org/10.1038/s41392-021-00558-8
doi: 10.1038/s41392-021-00558-8
pubmed: 33774649
pmcid: 7997800
Cambier S, Metzemaekers M, de Carvalho AC, Nooyens A, Jacobs C, Vanderbeke L, Malengier-Devlies B, Gouwy M, Heylen E, Meersseman P et al (2022) Atypical response to bacterial coinfection and persistent neutrophilic bronchoalveolar inflammation distinguish critical COVID-19 from influenza. JCI Insight 7:e155055. https://doi.org/10.1172/jci.insight.155055
doi: 10.1172/jci.insight.155055
pubmed: 34793331
pmcid: 8765057
Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, Cheng L, Li J, Wang X, Wang F et al (2020) Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med 26:842–844. https://doi.org/10.1038/s41591-020-0901-9
doi: 10.1038/s41591-020-0901-9
pubmed: 32398875
Jerke U, Hernandez DP, Beaudette P, Korkmaz B, Dittmar G, Kettritz R (2015) Neutrophil serine proteases exert proteolytic activity on endothelial cells. Kidney Int 88:764–775. https://doi.org/10.1038/ki.2015.159
doi: 10.1038/ki.2015.159
pubmed: 26061547
Fischer M, Kuckenberg M, Kastilan R, Muth J, Gebhardt C (2015) Novel in vitro inhibitory functions of potato tuber proteinaceous inhibitors. Mol Genet Genomics 290:387–398. https://doi.org/10.1007/s00438-014-0906-5
doi: 10.1007/s00438-014-0906-5
pubmed: 25260821
Valueva TA, Revina TA, Mosolov VV (1997) Potato tuber protein proteinase inhibitors belonging to the Kunitz soybean inhibitor family. Biochem 62(12):1367–74
Vandooren J, Van den Steen PE, Opdenakker G (2013) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): the next decade. Crit Rev Biochem Mol Biol 48:222–272. https://doi.org/10.3109/10409238.2013.770819
doi: 10.3109/10409238.2013.770819
pubmed: 23547785
Finlay JB, Brann DH, Abi Hachem R, Jang DW, Oliva AD, Ko T, Gupta R, Wellford SA, Moseman EA, Jang SS et al (2022) Persistent post-COVID-19 smell loss is associated with immune cell infltration and altered gene expression in olfactory epithelium. Sci Transl Med 14(676):eadd0484. https://doi.org/10.1126/scitranslmed.add0484
doi: 10.1126/scitranslmed.add0484
pubmed: 36542694
pmcid: 10317309
Starch Europe (2021) Joint Starch Europe – CESPU Statement: The EU Potato Starch Value Chain, Sustainability and the EU Green Deal. https://starch.eu/priority/joint-starch-europe-cespu-statement-the-eu-potato-starch-value-chain-sustainability-and-the-eu-green-deal/ . Accessed 21 Nov 2022
Pęksa A, Miedzianka J (2021) Potato industry by-products as a source of protein with beneficial nutritional, functional, health-promoting and antimicrobial properties. Appl Sci 11:3497. https://doi.org/10.3390/app11083497
doi: 10.3390/app11083497
Sugano H (1997) New production method of camostat mesylate. Japan Patent JPH09309873A, 2 Feb 1997
Bhadra S, Ghosh SC, Adimurthy S, Kumar JS, Chiranjit, Rawat D (2020) Process for the preparation of camostat mesylate intermediates. India Patent IN202011047949, 02-11-2020
You X, Li Y, Zhang G, Wang X, Yan Y, Wei W (2013) A kind of preparation method of nafamostat mesylate. China Patent CN103641749B, 10 Feb 2016
Norris K, Norris F, Søren Erik B (1988) Aprotinin homologues and process for the production of aprotinin and aprotinin homologues in yeast. WO Patent WO1989001968, 3 Sept 1989
Norris K, Petersen LC (1989) Aprotinin analogues and process for the production thereof. Europe Patent EP0339942A2, 2 Sept 1989
Valueva TA, Kladnitskaya GV, Mosolov VV (1996) A novel human leukocyte elastase inhibitor from duck egg white. Immunopharmacology 32:108–110. https://doi.org/10.1016/0162-3109(95)00066-6
doi: 10.1016/0162-3109(95)00066-6
pubmed: 8796282
International Organization for Standardization ISO (2012) Standard 14902:2001. Animal feedingstuffs—determination of trypsininhibitor activity of soya products. Approved Oct 2001; Reapproved Aug 2012. Geneva. https://www.iso.org/obp/ui/en/#iso:std:iso:14902:ed-1:v1:en
Van den Steen PE, Van Aelst I, Hvidberg V, Piccard H, Fiten P, Jacobsen C, Moestrup SK, Fry S, Royle L, Wormald MR et al (2006) The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. J Biol Chem 281:18626–18637. https://doi.org/10.1074/jbc.M512308200
doi: 10.1074/jbc.M512308200
pubmed: 16672230
De Buck M, Berghmans N, Pörtner N, Vanbrabant L, Cockx M, Struyf S, Opdenakker G, Proost P, Van Damme J, Gouwy M (2015) Serum amyloid A1α induces paracrine IL-8/CXCL8 via TLR2 and directly synergizes with this chemokine via CXCR2 and formyl peptide receptor 2 to recruit neutrophils. J Leukoc Biol 98:1049–1060. https://doi.org/10.1189/jlb.3A0315-085R
doi: 10.1189/jlb.3A0315-085R
pubmed: 26297794
Uniprot (2011) Proteomes - Solanum tuberosum (Potato). https://www.uniprot.org/proteomes/UP000011115 . Accessed 15 Nov 2021
Xu X, Pan S, Cheng S, Zhang B, Mu D, Ni P, Zhang G, Yang S, Li R, Wang J et al (2011) Genome sequence and analysis of the tuber crop potato. Nature 475:189–195. https://doi.org/10.1038/nature10158
doi: 10.1038/nature10158
pubmed: 21743474