Hymecromone: a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression.
Hymecromone: a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression.
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Hymecromone：一种临床处方透明质酸抑制剂，可有效阻止 COVID-19 进展
DOI：
10.1038/s41392-022-00952-w
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发表时间：
2022-03-18
影响因子：
39.3
通讯作者：
Lu H
中科院分区：
文献类型：
--
作者：
Yang S;Ling Y;Zhao F;Li W;Song Z;Wang L;Li Q;Liu M;Tong Y;Chen L;Ru D;Zhang T;Zhou K;Zhang B;Xu P;Yang Z;Li W;Song Y;Xu J;Zhu T;Shan F;Yu W;Lu H
目前，临床上除地塞米松外，尚无治疗COVID-19的有效药物。我们之前揭示了 SARS-CoV-2 的人类相同序列通过上调透明质酸 (HA) 来促进 COVID-19 的进展。作为HA合成的抑制剂，hymecromone是一种批准用于治疗胆道痉挛的处方药。在这里，我们的目的是研究HA与COVID-19之间的关系，并评估hymecromone对COVID-19的治疗效果。首先，HA与临床参数密切相关，包括淋巴细胞（n = 158；r = −0.50；P < 0.0001）、C反应蛋白（n = 156；r = 0.55；P < 0.0001）、D-二聚体(n = 154；r = 0.38；P < 0.0001)和纤维蛋白原(n = 152；r = 0.37；P < 0.0001)，以及质量(n = 78； r = 0.43；P < 0.0001) 和毛玻璃混浊的体积 (n = 78；r = 0.41；P = 0.0002)，质量 (n = 78；r = 0.48； P < 0.0001）和低透明质酸水平（HA < 48.43ng/mL）患者的实变体积（n = 78；r = 0.47；P < 0.0001）。此外，透明质酸可直接引起小鼠肺部病变。此外，hymecromone 通过下调 HAS2/HAS3 表达显着降低 HA。此外，hymecromone治疗组89%的患者出现肺部病灶吸收，而对照组仅有42%的患者出现肺部病灶吸收（P < 0.0001）。此外，hymecromone 治疗组患者 (n = 8) 的淋巴细胞恢复速度比对照组 (n = 5) 更快 (P < 0.05)。这些研究结果表明，hymecromone 是一种很有前途的治疗 COVID-19 的药物，值得我们进一步努力确定其在更大群体中的效果。
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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DOI：
10.1056/nejmoa2022926
发表时间：
2020-11-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
RECOVERY Collaborative Group;Horby P;Mafham M;Linsell L;Bell JL;Staplin N;Emberson JR;Wiselka M;Ustianowski A;Elmahi E;Prudon B;Whitehouse T;Felton T;Williams J;Faccenda J;Underwood J;Baillie JK;Chappell LC;Faust SN;Jaki T;Jeffery K;Lim WS;Montgomery A;Rowan K;Tarning J;Watson JA;White NJ;Juszczak E;Haynes R;Landray MJ
通讯作者：
Landray MJ
影响因子：
--
作者：
Shi W;Peng X;Liu T;Cheng Z;Lu H;Yang S;Zhang J;Wang M;Gao Y;Shi Y;Zhang Z;Shan F
通讯作者：
Shan F
针对SARS-COV-2主要蛋白酶作为Covid-19的药物开发的最新进展。
影响因子：
5
作者：
Cui W;Yang K;Yang H
通讯作者：
Yang H
影响因子：
16.1
作者：
Liang J;Jiang D;Noble PW
通讯作者：
Noble PW
影响因子：
4.4
作者：
Ruffell, Brian;Johnson, Pauline
通讯作者：
Johnson, Pauline