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Updated: Nov 26, 2025
Detection of SARS-CoV-2 Receptor-Binding Domain Antibody using a HiBiT-Based Bioreporter
Published on: August 12, 2021
HMGB1 as a potential biomarker and therapeutic target for severe COVID-19
Ruochan Chen1,2, Yan Huang1,2, Jun Quan1,2
1Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Insights
High mobility group box 1 (HMGB1) is elevated in severe COVID-19 and promotes viral entry by increasing ACE2 expression. Inhibiting the HMGB1-AGER pathway offers a potential therapeutic strategy for COVID-19 treatment.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Severe COVID-19 is linked to immune overactivation, cytokine storm syndrome, and multi-organ failure.
- High mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP), is a key mediator of lethal inflammation.
Purpose of the Study:
- To investigate the role of HMGB1 in COVID-19 pathogenesis.
- To explore HMGB1 as a therapeutic target for COVID-19.
Main Methods:
- Measured serum HMGB1 levels in severe COVID-19 patients.
- Investigated the effect of exogenous HMGB1 on ACE2 expression in alveolar epithelial cells.
- Utilized genetic (AGER siRNA) and pharmacological inhibitors (glycyrrhizin, chloroquine, hydroxychloroquine, FPS-ZM1) to block the HMGB1-AGER pathway.
Main Results:
- Serum HMGB1 levels were significantly elevated in severe COVID-19 patients (189.40 ± 140.88 ng/ml).
- Exogenous HMGB1 increased ACE2 expression in alveolar epithelial cells via an AGER-dependent mechanism.
- Inhibition of the HMGB1-AGER pathway effectively blocked ACE2 expression.
Conclusions:
- HMGB1 plays a crucial role in severe COVID-19 by upregulating ACE2 expression.
- HMGB1 inhibitors represent promising therapeutic candidates for treating COVID-19.
Abstract:
COVID-19 has attracted global attention due to its rapid spread around the world with substantial morbidity and associated mortality. Severe COVID-19 can be complicated by the acute respiratory distress syndrome, sepsis and septic shock leading to death. These complications are thought to result from an overactivation of the immune system, leading to a cytokine storm syndrome associated with multiple organ failure. Here, we report that high mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) and a central mediator of lethal inflammation, could be a potential target for innovative therapeutic strategies for COVID-19. Serum HMGB1 in severe COVID-19 patients is elevated (189.40 ± 140.88 ng/ml). Exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in an AGER-dependent manner. Importantly, genetic (using AGER siRNA) or pharmacological (using glycyrrhizin, chloroquine, hydroxychloroquine, and FPS-ZM1) inhibition of the HMGB1-AGER pathway blocks ACE2 expression. Thus, HMGB1 inhibitors are likewise promising drug candidates for the treatment of patients suffering from COVID-19.
