Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection.
Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection.
复制标题
甘草中的天然三萜类化合物可有效抑制 SARS-CoV-2 感染
DOI：
10.1016/j.jare.2021.11.012
复制
发表时间：
2022-03
影响因子：
10.7
通讯作者：
Ye M
中科院分区：
文献类型：
--
作者：
Yi Y;Li J;Lai X;Zhang M;Kuang Y;Bao YO;Yu R;Hong W;Muturi E;Xue H;Wei H;Li T;Zhuang H;Qiao X;Xiang K;Yang H;Ye M
本工作从中草药甘草中筛选出125种化合物。甘草皂苷A3和甘草次酸分别靶向NSP7蛋白和刺突蛋白受体结合域，有效地抑制SARS-CoV-2的感染，EC50值分别为0.075和3.17um。甘草皂苷A3和甘草次酸分别通过靶向NSP7和S-RBD抑制SARS-CoV-2。这些化合物的药物潜力被细胞模型和PK研究所证实。示范了草药的“多组分、多目标”行动模式。甘草三萜类化合物有望成为抗SARS-CoV-2药物开发的候选药物。由严重急性呼吸综合征冠状病毒(SARS-CoV-2)引发的全球新冠肺炎疫情是一场重大的突发公共卫生事件。发现抗病毒药物候选药物是防治新冠肺炎的当务之急。本工作旨在从传统中草药甘草中发现天然的SARS-CoV-2抑制剂。我们从乌拉尔甘草中筛选出125个小分子。(甘草)通过针对SARS-CoV-2刺突蛋白受体结合域(RBD)的虚拟配体筛选。进一步采用ELISA法、SPR法、荧光素酶测定法、抗病毒测定法和药代动力学研究对潜在的HIT化合物进行了评价。三萜甘草皂苷A3(A3)和甘草次酸(GA)对SARS-CoV-2感染有较强的抑制作用，EC50分别为75 nM和3.17µM。此外，我们还发现A3主要针对NSP7蛋白，GA与SARS-CoV-2的刺突蛋白RBD结合。在这项工作中，我们发现甘草中的GA和A3通过影响病毒的进入和复制而有效地抑制SARS-CoV-2的感染。我们的发现表明，这些三萜类化合物可能有助于甘草治疗新冠肺炎的临床疗效，并可能成为抗病毒药物开发的有前途的候选药物。
This work screened 125 compounds from the Chinese herbal medicine licorice. Licorice-saponin A3 and glycyrrhetinic acid potently inhibit SARS-CoV-2 infection, targeting the nsp7 protein and the spike protein receptor binding domain, respectively, with EC50 of 0.075 and 3.17 µM. Systemic approach to discover SARS-CoV-2 inhibitors from the herbal medicine licorice. Licorice-saponin A3 and glycyrrhetinic acid inhibit SARS-CoV-2 by targeting nsp7 and the S-RBD, respectively. Drug potential of these compounds was confirmed by cell models and PK studies. The “multi-component, multi-target” mode of action was demonstrated for herbal medicines. Licorice triterpenoids could be promising candidates for anti-SARS-CoV-2 drug development. The COVID-19 global epidemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a great public health emergency. Discovering antiviral drug candidates is urgent for the prevention and treatment of COVID-19. This work aims to discover natural SARS-CoV-2 inhibitors from the traditional Chinese herbal medicine licorice. We screened 125 small molecules from Glycyrrhiza uralensis Fisch. (licorice, Gan-Cao) by virtual ligand screening targeting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Potential hit compounds were further evaluated by ELISA, SPR, luciferase assay, antiviral assay and pharmacokinetic study. The triterpenoids licorice-saponin A3 (A3) and glycyrrhetinic acid (GA) could potently inhibit SARS-CoV-2 infection, with EC50 of 75 nM and 3.17 µM, respectively. Moreover, we reveal that A3 mainly targets the nsp7 protein, and GA binds to the spike protein RBD of SARS-CoV-2. In this work, we found GA and A3 from licorice potently inhibit SARS-CoV-2 infection by affecting entry and replication of the virus. Our findings indicate that these triterpenoids may contribute to the clinical efficacy of licorice for COVID-19 and could be promising candidates for antiviral drug development.
登录
查看更多内容
基于人体暴露和ACE2生物色谱筛选鉴定中药连花清瘟胶囊潜在抗COVID-19药理成分
DOI：
10.1016/j.apsb.2020.10.002
发表时间：
2021-01
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Chen X;Wu Y;Chen C;Gu Y;Zhu C;Wang S;Chen J;Zhang L;Lv L;Zhang G;Yuan Y;Chai Y;Zhu M;Wu C
通讯作者：
Wu C
影响因子：
14.5
作者：
Luo, Lu;Jiang, Jingwen;Chen, Shilin
通讯作者：
Chen, Shilin
DOI：
10.1126/science.abd5223
发表时间：
2020-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Turoňová B;Sikora M;Schürmann C;Hagen WJH;Welsch S;Blanc FEC;von Bülow S;Gecht M;Bagola K;Hörner C;van Zandbergen G;Landry J;de Azevedo NTD;Mosalaganti S;Schwarz A;Covino R;Mühlebach MD;Hummer G;Krijnse Locker J;Beck M
通讯作者：
Beck M
影响因子：
5
作者：
Sevajol M;Subissi L;Decroly E;Canard B;Imbert I
通讯作者：
Imbert I
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD