The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells

Allicin (diallyl thiosulfinate) is the major thiol-reactive organosulfur compound produced by garlic plants (Allium sativum) upon tissue damage. Allicin exerts its strong antimicrobial activity against bacteria and fungi via S-thioallylation of protein thiols and low molecular weight thiols. Here, w...

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Autores principales: Mösbauer, Kirstin, Fritsch, Verena Nadin, Adrian, Lorenz, Bernhardt, Jörg, Gruhlke, Martin Clemens Horst, Slusarenko, Alan John, Niemeyer, Daniela, Antelmann, Haike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581659/
https://www.ncbi.nlm.nih.gov/pubmed/34777295
http://dx.doi.org/10.3389/fmicb.2021.746795
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author Mösbauer, Kirstin
Fritsch, Verena Nadin
Adrian, Lorenz
Bernhardt, Jörg
Gruhlke, Martin Clemens Horst
Slusarenko, Alan John
Niemeyer, Daniela
Antelmann, Haike
author_facet Mösbauer, Kirstin
Fritsch, Verena Nadin
Adrian, Lorenz
Bernhardt, Jörg
Gruhlke, Martin Clemens Horst
Slusarenko, Alan John
Niemeyer, Daniela
Antelmann, Haike
author_sort Mösbauer, Kirstin
collection PubMed
description Allicin (diallyl thiosulfinate) is the major thiol-reactive organosulfur compound produced by garlic plants (Allium sativum) upon tissue damage. Allicin exerts its strong antimicrobial activity against bacteria and fungi via S-thioallylation of protein thiols and low molecular weight thiols. Here, we investigated the effect of allicin on SARS-CoV-2 infected Vero E6 and Calu-3 cells. Toxicity tests revealed that Calu-3 cells showed greater allicin tolerance, probably due to >4-fold higher GSH levels compared to the very sensitive Vero E6 cells. Exposure of infected Vero E6 and Calu-3 cells to biocompatible allicin doses led to a ∼60–70% decrease of viral RNA and infectious viral particles. Label-free quantitative proteomics was used to investigate the changes in the Calu-3 proteome after SARS-CoV-2 infection and the effect of allicin on the host-virus proteome. SARS-CoV-2 infection of Calu-3 cells caused a strong induction of the antiviral interferon-stimulated gene (ISG) signature, including several antiviral effectors, such as cGAS, Mx1, IFIT, IFIH, IFI16, IFI44, OAS, and ISG15, pathways of vesicular transport, tight junctions (KIF5A/B/C, OSBPL2, CLTCL1, and ARHGAP17) and ubiquitin modification (UBE2L3/5), as well as reprogramming of host metabolism, transcription and translation. Allicin treatment of infected Calu-3 cells reduced the expression of IFN signaling pathways and ISG effectors and reverted several host pathways to levels of uninfected cells. Allicin further reduced the abundance of the structural viral proteins N, M, S and ORF3 in the host-virus proteome. In conclusion, our data demonstrate the antiviral and immunomodulatory activity of biocompatible doses of allicin in SARS-CoV-2-infected cell cultures. Future drug research should be directed to exploit the thiol-reactivity of allicin derivatives with increased stability and lower human cell toxicity as antiviral lead compounds.
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spelling pubmed-85816592021-11-12 The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells Mösbauer, Kirstin Fritsch, Verena Nadin Adrian, Lorenz Bernhardt, Jörg Gruhlke, Martin Clemens Horst Slusarenko, Alan John Niemeyer, Daniela Antelmann, Haike Front Microbiol Microbiology Allicin (diallyl thiosulfinate) is the major thiol-reactive organosulfur compound produced by garlic plants (Allium sativum) upon tissue damage. Allicin exerts its strong antimicrobial activity against bacteria and fungi via S-thioallylation of protein thiols and low molecular weight thiols. Here, we investigated the effect of allicin on SARS-CoV-2 infected Vero E6 and Calu-3 cells. Toxicity tests revealed that Calu-3 cells showed greater allicin tolerance, probably due to >4-fold higher GSH levels compared to the very sensitive Vero E6 cells. Exposure of infected Vero E6 and Calu-3 cells to biocompatible allicin doses led to a ∼60–70% decrease of viral RNA and infectious viral particles. Label-free quantitative proteomics was used to investigate the changes in the Calu-3 proteome after SARS-CoV-2 infection and the effect of allicin on the host-virus proteome. SARS-CoV-2 infection of Calu-3 cells caused a strong induction of the antiviral interferon-stimulated gene (ISG) signature, including several antiviral effectors, such as cGAS, Mx1, IFIT, IFIH, IFI16, IFI44, OAS, and ISG15, pathways of vesicular transport, tight junctions (KIF5A/B/C, OSBPL2, CLTCL1, and ARHGAP17) and ubiquitin modification (UBE2L3/5), as well as reprogramming of host metabolism, transcription and translation. Allicin treatment of infected Calu-3 cells reduced the expression of IFN signaling pathways and ISG effectors and reverted several host pathways to levels of uninfected cells. Allicin further reduced the abundance of the structural viral proteins N, M, S and ORF3 in the host-virus proteome. In conclusion, our data demonstrate the antiviral and immunomodulatory activity of biocompatible doses of allicin in SARS-CoV-2-infected cell cultures. Future drug research should be directed to exploit the thiol-reactivity of allicin derivatives with increased stability and lower human cell toxicity as antiviral lead compounds. Frontiers Media S.A. 2021-10-28 /pmc/articles/PMC8581659/ /pubmed/34777295 http://dx.doi.org/10.3389/fmicb.2021.746795 Text en Copyright © 2021 Mösbauer, Fritsch, Adrian, Bernhardt, Gruhlke, Slusarenko, Niemeyer and Antelmann. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Mösbauer, Kirstin
Fritsch, Verena Nadin
Adrian, Lorenz
Bernhardt, Jörg
Gruhlke, Martin Clemens Horst
Slusarenko, Alan John
Niemeyer, Daniela
Antelmann, Haike
The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells
title The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells
title_full The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells
title_fullStr The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells
title_full_unstemmed The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells
title_short The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells
title_sort effect of allicin on the proteome of sars-cov-2 infected calu-3 cells
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581659/
https://www.ncbi.nlm.nih.gov/pubmed/34777295
http://dx.doi.org/10.3389/fmicb.2021.746795
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