Kirstin Mosbauer and colleagues in their recent paper showed that allicin efficiently inhibit SARS-CoV-2 replication and infectivity in Vero E6 and Calu-3 cell lines
There have been many drugs approved by FDA in clinical trials for treatment of COVID-19 like remdesivir, lopinavir/ritonavir and favipiravir. Apart from drugs, functional food based on herbal medicine is suggested as prophylaxis to prevent COVID-19 outcome due to their immunomodulatory, antioxidant, anticancer, antimicrobial and antiviral activities.
For example, garlic has been used for millennia in the treatment of a variety of human diseases and metabolic disorders. However, a review of the scientific literature suggests it could also have value as an inhalation therapy in the treatment of pulmonary infections caused by COVID-19 infection, and associated secondary bacterial infections, a significant cause of mortality in hospitalised patients.
Allicin, the principal active ingredient in garlic, has marked antimicrobial and antifungal properties and is active against many viruses including coronavirus (CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV).
While the antiviral effect of allicin has been studied against several viruses that cause respiratory tract infections, including influenza, SARSCoV and rhinovirus, mechanistic insights on its proposed antiviral effects against SARS-CoV-2 in the infected host cell are lacking. Thus, Kirstin Mosbauer and colleagues now investigated the antiviral effect of allicin against SARS-CoV-2 in infected Vero E6 kidney cells and Calu-3 lung cells.
They found that, only the addition of 50 µM allicin to infected Vero E6 cells led to a significant 70% decrease in the amount of infectious virus particles, whereas, virus plaque assays and qRT-PCR results showed an almost complete >99% inhibition of SARS-COV-2 replication after exposure of 75 µM allicin, supporting the strong antiviral activity of allicin in infected Vero E6 cells.
Additionally, the antiviral effects of biocompatible doses of allicin were analyzed in the human lung cell line Calu-3. After infection with SARS-CoV-2 at a multiplicity of infection (MOI) of 0.01 and 0.005, Calu-3 cells were treated with biocompatible doses of 100 and 200 µM allicin, respectively. It has been found that, the treatment of infected Calu-3 cells with 100 µM allicin did not significantly inhibit viral replication. However, exposure of infected Calu-3 cells to 200 µM allicin led to a significant >60 % decrease of viral RNA and a >65% reduction of infectious particles. These results were further supported by microscopy imaging in which, allicin partially protected the cells against the cellular damage of Calu-3 cells caused by SARS-CoV-2 infection.
“Taken together, our results show that allicin exerts a strong antiviral effect and inhibits SARS-CoV-2 replication in both the primate kidney-derived cell line Vero E6 and the human lung cell line Calu-3. In addition, the different allicin susceptibilities in these cell lines were caused by different intracellular Glutathione (GSH) levels”
Moreover, they used Label-free quantitative (LFQ) proteomics to further investigate the changes in proteome of Calu-3 cells caused by SARS-CoV-2 infection and the effect of allicin. They found that, allicin strongly affected virus-responsive expression of JAK/STAT, MAPK, PI3K/Akt and Ras signaling pathways, interferon (IFN) and interferon-stimulated gene (ISG) effectors, transcription, splicing, translation, ubiquitination, vesicular transport, tight junctions as well as glycan, lipid and nucleotide metabolism. Thus, their results confirm the antiviral and protective effect of allicin in host cells, supported by a decreased cellular damage of allicin-treated infected Calu-3 cells.
“Allicin exerts a beneficial effect as an antiviral and immunomodulatory compound in cell lines and could be utilized as a supportive therapy for the treatment of COVID-19.”— concluded authors of the study
Featured image: Schematic of viral RNA recognition, activation of the IFN and ISG signaling pathways (A) and antiviral functions of the identified ISG effectors (B). A) SARS-CoV-2 enters host cells via endocytosis. RIG-I is a cytosolic receptor to recognize viral RNA. cGAS and OAS are ISG effectors that function as RNA sensors. RIG-I, IFIH and cGAS activate the mitochondrial antiviral-signaling protein (MAVS) and stimulator of IFN genes (STING), leading to phosphorylation of IFN responsive factors (e.g. IRF3), followed by IRF3 dimerization, translocation into the nucleus and transcriptional activation of IFN expression. IRF3 is negatively regulated by IFI44. RIG-I, MAVS and STING can be regulated by ubiquitination (UBE2) and ISGylation (ISG15). Type-I IFN a/ß bind to the IFNAR receptor, resulting in phosphorylation of signal transducers and activators of transcription (STAT1/2) by the JAK and TYK kinases. Phosphorylated STAT1/2 form dimers and bind to IRF9, which triggers transcription of IFN-stimulated genes (ISGs) in the nucleus. B) Antiviral ISG effectors affect different stages of the viral life cycle. Mx1 inhibits virus endocytosis and uncoating of the ribonucleocapsid. IFI16, OAS and IFIT function in viral RNA degradation and block translation. IFIT, ISG15, TRIM and UBEL inhibit transcription, replication, translation or virus assembly. FKBP4 promotes protein folding. Kinesins (KIFA/B/C), Clathrin (CLTCL1) and TUBAL3 are involved in transport of virus vesicles. ARHGAP17 facilitates the formation or repair of tight junctions. © K. Mösbauer et al.
Reference: Kirstin Mösbauer, Verena Nadin Fritsch, Lorenz Adrian, Jörg Bernhardt, Martin Clemens Horst Gruhlke, Alan John Slusarenko, Daniela Niemeyer, Haike Antelmann, “Allicin inhibits SARS-CoV-2 replication and abrogates the antiviral host response in the Calu-3 proteome”, bioRxiv 2021.05.15.444275; doi: https://doi.org/10.1101/2021.05.15.444275
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