Glycyrrhizin prevents SARS-CoV-2 S1 and Orf3a induced high mobility group box 1 (HMGB1) release and inhibits viral replication.
Cytokine
; 142: 155496, 2021 06.
Article
in English
| MEDLINE | ID: covidwho-1152317
ABSTRACT
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-1ß and extracellular HMGB1 levels. Glycyrrhizin mitigated viral proteins-induced lung cell pyroptosis and activation of macrophages. Heightened release of proinflammatory cytokines IL-1ß, 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Replication
/
Glycyrrhizic Acid
/
HMGB1 Protein
/
Spike Glycoprotein, Coronavirus
/
Viroporin Proteins
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Cytokine
Journal subject:
Allergy and Immunology
Year:
2021
Document Type:
Article
Affiliation country:
J.cyto.2021.155496
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