State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
J Adv Res. 2021 Nov 26;36:201-210. doi: 10.1016/j.jare.2021.11.012. eCollection 2022 Feb.
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 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 EC 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.
由严重急性呼吸系统综合征冠状病毒 2 型(SARS-CoV-2)引起的 COVID-19 全球疫情是一场重大的公共卫生紧急事件。发现抗病毒药物候选物对于 COVID-19 的预防和治疗至关重要。
本研究旨在从传统中药甘草中发现天然 SARS-CoV-2 抑制剂。
我们通过针对 SARS-CoV-2 刺突蛋白受体结合域(RBD)的虚拟配体筛选,从 Fisch.(甘草,甘草)中筛选了 125 种小分子。通过 ELISA、SPR、荧光素酶测定、抗病毒测定和药代动力学研究进一步评估潜在的命中化合物。
三萜甘草皂苷 A3(A3)和甘草酸(GA)能够强烈抑制 SARS-CoV-2 感染,EC50 分别为 75 nM 和 3.17 µM。此外,我们发现 A3 主要靶向 nsp7 蛋白,而 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,强烈抑制 SARS-CoV-2 感染。我们的研究结果表明,这些三萜类化合物可能有助于甘草治疗 COVID-19 的临床疗效,并且可能是有前途的抗病毒药物开发候选物。