期刊
CYTOKINE
卷 142, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2021.155496
关键词
SARS-CoV-2; COVID-19; HMGB1; Cytokine; Ferritin; Macrophages
资金
- NBRC (Department of Biotechnology, Government of India)
This study highlights the crucial role of HMGB1 in regulating COVID-19 pathogenesis and demonstrates that the inhibitor Glycyrrhizin can mitigate cellular perturbations and proinflammatory responses induced by SARS-CoV-2 viral proteins. Glycyrrhizin not only inhibits virus replication, but also dampens the release of proinflammatory cytokines, suggesting its potential as a therapeutic option for SARS-CoV-2 infection.
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-1? and extracellular HMGB1 levels. Glycyrrhizin mitigated viral proteins-induced lung cell pyroptosis and activation of macrophages. Heightened release of proinflammatory cytokines IL-1?, 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.
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