Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage.

Autor: Visser N; Department of Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands., Herreman LCM; Avebe Innovation Center Groningen, 9747 AW, Groningen, The Netherlands., Vandooren J; Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000, Louvain, Belgium., Pereira RVS; Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000, Louvain, Belgium., Opdenakker G; Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000, Louvain, Belgium., Spelbrink REJ; Avebe Innovation Center Groningen, 9747 AW, Groningen, The Netherlands., Wilbrink MH; Avebe Innovation Center Groningen, 9747 AW, Groningen, The Netherlands., Bremer E; Department of Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands., Gosens R; Department of Molecular Pharmacology, University Medical Center Groningen, 9713 GZ, Groningen, The Netherlands.; Groningen Research Institute for Asthma and COPD (GRIAC) Research Institute, University of Groningen, 9713 GZ, Groningen, The Netherlands., Nawijn MC; Groningen Research Institute for Asthma and COPD (GRIAC) Research Institute, University of Groningen, 9713 GZ, Groningen, The Netherlands.; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, The Netherlands., van der Ende-Metselaar HH; Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands., Smit JM; Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands., Laus MC; Avebe Innovation Center Groningen, 9747 AW, Groningen, The Netherlands., Laman JD; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, The Netherlands. j.d.laman@umcg.nl.
Jazyk: angličtina
Zdroj: Journal of molecular medicine (Berlin, Germany) [J Mol Med (Berl)] 2024 Apr; Vol. 102 (4), pp. 521-536. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1007/s00109-024-02423-x
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: