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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.
  • Mösbauer K; Institute of Virology, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Berlin, Germany.
  • Fritsch VN; German Centre for Infection Research (DZIF), Berlin, Germany.
  • Adrian L; Institute for Biology-Microbiology, Freie Universität Berlin, Berlin, Germany.
  • Bernhardt J; Department Environmental Biotechnology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany.
  • Gruhlke MCH; Fachgebiet Geobiotechnologie, Technische Universität Berlin, Berlin, Germany.
  • Slusarenko AJ; Institute for Microbiology, University of Greifswald, Greifswald, Germany.
  • Niemeyer D; Department of Plant Physiology, RWTH Aachen University, Aachen, Germany.
  • Antelmann H; Department of Plant Physiology, RWTH Aachen University, Aachen, Germany.
Front Microbiol ; 12: 746795, 2021.
Article in English | MEDLINE | ID: covidwho-1518504
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Language: English Journal: Front Microbiol Year: 2021 Document Type: Article Affiliation country: Fmicb.2021.746795

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Language: English Journal: Front Microbiol Year: 2021 Document Type: Article Affiliation country: Fmicb.2021.746795