PT - JOURNAL ARTICLE AU - Mösbauer, Kirstin AU - Fritsch, Verena Nadin AU - Adrian, Lorenz AU - Bernhardt, Jörg AU - Gruhlke, Martin Clemens Horst AU - Slusarenko, Alan John AU - Niemeyer, Daniela AU - Antelmann, Haike TI - Allicin inhibits SARS-CoV-2 replication and abrogates the antiviral host response in the Calu-3 proteome AID - 10.1101/2021.05.15.444275 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.05.15.444275 4099 - http://biorxiv.org/content/early/2021/06/24/2021.05.15.444275.short 4100 - http://biorxiv.org/content/early/2021/06/24/2021.05.15.444275.full AB - The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is a major health burden. Volatile garlic organosulfur compounds, such as the thiol-reactive allicin (diallyl thiosulfinate) exert strong antimicrobial activity against various respiratory pathogens. Here, we investigated the antiviral activity of allicin against SARS-CoV-2 in infected Vero E6 and Calu-3 lung cells. Calu-3 cells showed greater allicin tolerance due >4-fold increased GSH levels compared to Vero E6. However, biocompatible allicin doses efficiently inhibited viral replication in both cell lines. Proteome analyses of SARS-CoV-2 infected Calu-3 cells revealed a strong induction of the antiviral interferon-stimulated gene (ISG) signature (e.g. cGAS, Mx1, IFIT, IFIH, IFI16, IFI44, 2’5’OAS and ISG15), pathways of vesicular transport, tight junctions (KIF5A/B/C, OSBPL2, CLTC1, ARHGAP17) and ubiquitin modification (UBE2L3/5), as well as reprogramming of host metabolism, transcription and translation. Allicin abrogated the ISG host response and reverted the host cellular pathways to levels of uninfected Calu-3 cells, confirming the antiviral and immunomodulatory activity of allicin in the host proteome. Thus, biocompatible doses of allicin could be promising for protection of lung cells against SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.