Indole-3-carbinol in vitro antiviral activity against SARS-Cov-2 virus and in vivo toxicity.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
15 Dec 2022
15 Dec 2022
Historique:
received:
28
09
2022
accepted:
06
12
2022
revised:
30
11
2022
entrez:
15
12
2022
pubmed:
16
12
2022
medline:
16
12
2022
Statut:
epublish
Résumé
The effects of indole-3-carbinol (I3C) compound have been described deeply as antitumor drug in multiple cancers. Herein, I3C compound was tested for toxicity and antiviral activity against SARS-CoV-2 infection. Antiviral activity was assessed in vitro in both in VeroE6 cell line and human Lung Organoids (hLORGs) where I3C exhibited a direct anti-SARS-CoV-2 replication activity with an antiviral effect and a modulation of the expression of genes implicated in innate immunity and inflammatory response was observed at 16.67 μM. Importantly, we further show the I3C is also effective against the SARS-CoV-2 Omicron variant. In mouse model, instead, we assessed possible toxicity effects of I3C through two different routes of administration: intragastrically (i.g.) and intraperitoneally (i.p.). The LD50 (lethal dose 50%) values in mice were estimated to be: 1410 and 1759 mg/kg i.g.; while estimated values for i.p. administration were: 444.5 mg/kg and 375 mg/kg in male and female mice, respectively. Below these values, I3C (in particular at 550 mg/kg for i.g. and 250 mg/kg for i.p.) induces neither death, nor abnormal toxic symptoms as well as no histopathological lesions of the tissues analysed. These tolerated doses are much higher than those already proven effective in pre-clinical cancer models and in vitro experiments. In conclusion, I3C exhibits a significant antiviral activity, and no toxicity effects were recorded for this compound at the indicated doses, characterizing it as a safe and potential antiviral compound. The results presented in this study could provide experimental pre-clinical data necessary for the start of human clinical trials with I3C for the treatment of SARS-CoV-2 and beyond.
Identifiants
pubmed: 36522315
doi: 10.1038/s41420-022-01280-2
pii: 10.1038/s41420-022-01280-2
pmc: PMC9751508
doi:
Types de publication
Journal Article
Langues
eng
Pagination
491Subventions
Organisme : Regione Lazio (Region of Lazio)
ID : A0375-2020-36663
Organisme : Ministero della Salute (Ministry of Health, Italy)
ID : Ricerca Corrente linea 1
Organisme : Ministero della Salute (Ministry of Health, Italy)
ID : Ricerca corrente linea 1
Informations de copyright
© 2022. The Author(s).
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