Hymecromone: a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression

• Published in: Signal transduction and targeted therapy Vol. 7; no. 1; p. 91
• Main Authors: Yang, Shuai, Ling, Yun, Zhao, Fang, Li, Wei, Song, Zhigang, Wang, Lu, Li, Qiuting, Liu, Mengxing, Tong, Ying, Chen, Lu, Ru, Daoping, Zhang, Tongsheng, Zhou, Kaicheng, Zhang, Baolong, Xu, Peng, Yang, Zhicong, Li, Wenxuan, Song, Yuanlin, Xu, Jianqing, Zhu, Tongyu, Shan, Fei, Yu, Wenqiang, Lu, Hongzhou
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18-03-2022; Nature Publishing Group
• Subjects: 692/308/575; 692/699/255; C-reactive protein; Cancer Research; Cell Biology; Coronaviruses; COVID-19; Dexamethasone; Fibrinogen; Hyaluronic acid; Internal Medicine; Lungs; Lymphocytes; Medicine; Medicine & Public Health; Oncology; Pathology; Patients; Pulmonary lesions; Severe acute respiratory syndrome coronavirus 2
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-022-00952-w

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.