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Hymecromone: a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression
Shuai Yang1, Yun Ling2, Fang Zhao3
1Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute Shanghai Medical College, Fudan University, Shanghai, P. R. China.
Insights
Hymecromone, an inhibitor of hyaluronic acid (HA) synthesis, shows promise in treating COVID-19. This study found HA correlates with COVID-19 severity and that hymecromone effectively reduced HA levels and improved pulmonary lesion absorption in patients.
Area of Science:
- Biomedical research
- Infectious diseases
- Pharmacology
Background:
- Limited effective treatments exist for severe COVID-19 beyond dexamethasone.
- SARS-CoV-2 upregulates hyaluronic acid (HA), a factor in COVID-19 progression.
- Hymecromone, an approved drug, inhibits HA synthesis and is used for biliary spasm.
Purpose of the Study:
- To investigate the relationship between hyaluronic acid (HA) and COVID-19.
- To evaluate the therapeutic potential of hymecromone in COVID-19 patients.
Main Methods:
- Correlational analysis of HA levels with clinical parameters and radiological findings in COVID-19 patients.
- Assessment of hymecromone's effect on HA synthesis by measuring HAS2/HAS3 expression.
- Clinical trial comparing pulmonary lesion absorption and lymphocyte recovery in COVID-19 patients treated with hymecromone versus a control group.
Main Results:
- Hyaluronic acid (HA) levels significantly correlated with clinical indicators of COVID-19 severity, including lymphocytes, C-reactive protein, D-dimer, and fibrinogen.
- Elevated HA levels were associated with increased ground-glass opacity and consolidation in lung imaging.
- Hymecromone treatment significantly reduced HA levels by downregulating HAS2/HAS3 expression.
- 89% of patients receiving hymecromone showed pulmonary lesion absorption, compared to 42% in the control group (P < 0.0001).
- Lymphocyte recovery was faster in the hymecromone-treated group.
Conclusions:
- Hyaluronic acid (HA) plays a significant role in COVID-19 progression and severity.
- Hymecromone demonstrates therapeutic potential for COVID-19 by reducing HA and improving clinical outcomes.
- Further investigation in larger cohorts is warranted to confirm hymecromone's efficacy as a COVID-19 treatment.
Abstract:
Currently, there is no effective drugs for treating clinically COVID-19 except dexamethasone. We previously revealed that human identical sequences of SARS-CoV-2 promote the COVID-19 progression by upregulating hyaluronic acid (HA). As the inhibitor of HA synthesis, hymecromone is an approved prescription drug used for treating biliary spasm. Here, we aimed to investigate the relation between HA and COVID-19, and evaluate the therapeutic effects of hymecromone on COVID-19. Firstly, HA was closely relevant to clinical parameters, including lymphocytes (n = 158; r = -0.50; P < 0.0001), C-reactive protein (n = 156; r = 0.55; P < 0.0001), D-dimer (n = 154; r = 0.38; P < 0.0001), and fibrinogen (n = 152; r = 0.37; P < 0.0001), as well as the mass (n = 78; r = 0.43; P < 0.0001) and volume (n = 78; r = 0.41; P = 0.0002) of ground-glass opacity, the mass (n = 78; r = 0.48; P < 0.0001) and volume (n = 78; r = 0.47; P < 0.0001) of consolidation in patient with low level of hyaluronan (HA < 48.43 ng/mL). Furthermore, hyaluronan could directly cause mouse pulmonary lesions. Besides, hymecromone remarkably reduced HA via downregulating HAS2/HAS3 expression. Moreover, 89% patients with hymecromone treatment had pulmonary lesion absorption while only 42% patients in control group had pulmonary lesion absorption (P < 0.0001). In addition, lymphocytes recovered more quickly in hymecromone-treated patients (n = 8) than control group (n = 5) (P < 0.05). These findings suggest that hymecromone is a promising drug for COVID-19 and deserves our further efforts to determine its effect in a larger cohort.
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