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Glycyrrhizin prevents SARS-CoV-2 S1 and Orf3a induced high mobility group box 1 (HMGB1) release and inhibits viral replication.
Gowda, Pruthvi; Patrick, Shruti; Joshi, Shanker Datt; Kumawat, Rajesh Kumar; Sen, Ellora.
  • Gowda P; National Brain Research Centre, Manesar, Gurugram, Haryana 122 052, India.
  • Patrick S; National Brain Research Centre, Manesar, Gurugram, Haryana 122 052, India.
  • Joshi SD; National Brain Research Centre, Manesar, Gurugram, Haryana 122 052, India.
  • Kumawat RK; National Brain Research Centre, Manesar, Gurugram, Haryana 122 052, India.
  • Sen E; National Brain Research Centre, Manesar, Gurugram, Haryana 122 052, India. Electronic address: ellora@nbrc.ac.in.
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.
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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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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