Glycyrrhizin prevents SARS-CoV-2 S1 and Orf3a induced high mobility group box 1 (HMGB1) release and inhibits viral replication.
COVID-19
Cytokine
Ferritin
HMGB1
Macrophages
SARS-CoV-2
Journal
Cytokine
ISSN: 1096-0023
Titre abrégé: Cytokine
Pays: England
ID NLM: 9005353
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
01
11
2020
revised:
04
03
2021
accepted:
05
03
2021
pubmed:
28
3
2021
medline:
20
4
2021
entrez:
27
3
2021
Statut:
ppublish
Résumé
Efforts to understand host factors critical for COVID-19 pathogenesis have identified high mobility group box 1 (HMGB1) to be crucial for regulating susceptibility to SARS-CoV-2. COVID-19 disease severity is correlated with heightened inflammatory responses, and HMGB1 is an important extracellular mediator in inflammation processes.In this study, we evaluated the effect of HMGB1 inhibitor Glycyrrhizin on the cellular perturbations in lung cells expressing SARS-CoV-2 viral proteins. Pyroptosis in lung cells transfected with SARS-CoV-2 S-RBD and Orf3a, was accompanied by elevation of IL-1β and extracellular HMGB1 levels. Glycyrrhizin mitigated viral proteins-induced lung cell pyroptosis and activation of macrophages. Heightened release of proinflammatory cytokines IL-1β, IL-6 and IL-8, as well as ferritin from macrophages cultured in conditioned media from lung cells expressing SARS-CoV-2 S-RBD and Orf3a was attenuated by glycyrrhizin. Importantly, Glycyrrhizin inhibited SARS-CoV-2 replication in Vero E6 cells without exhibiting cytotoxicity at high doses. The dual ability of Glycyrrhizin to concomitantly halt virus replication and dampen proinflammatory mediators might constitute a viable therapeutic option in patients with SARS-CoV-2 infection.
Identifiants
pubmed: 33773396
pii: S1043-4666(21)00076-4
doi: 10.1016/j.cyto.2021.155496
pmc: PMC7953444
pii:
doi:
Substances chimiques
HMGB1 Protein
0
HMGB1 protein, human
0
ORF3a protein, SARS-CoV-2
0
Spike Glycoprotein, Coronavirus
0
Viroporin Proteins
0
spike protein, SARS-CoV-2
0
Glycyrrhizic Acid
6FO62043WK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
155496Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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