Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection

Yang, Yi; Li, Junhua; Lai, Xinyuan; Zhang, Meng; Kuang, Yi; Bao, Yang-Oujie; Yu, Rong; Hong, Wei; Muturi, Ephantus J.; Xue, Heng; Wei, Hongping; Li, Tong; Zhang, Hui; Qiao, Xue; Xiang, Kuanhui; Yang, Hang

doi:10.1016/j.jare.2021.11.012

Cited by 68 publications

(62 citation statements)

References 39 publications

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“…Many studies have shown that herbal medicine offers multi-organ protection against SARS-CoV-2 (46). Ye et al (47) illustrated that licoricesaponin A3 and glycyrrhetinic acid, triterpenoids isolated from Gan-Cao, have strong inhibitory potency against SARS-CoV-2 infection at EC 50 values of 75 nM against the SARS-CoV-2 nsp7 protein and 3.17 µM against the Spike protein. In the COVID-19 era, small-molecule inhibitors and traditional medicine have a distinct advantage and should be shared between laboratories.…”

Section: Discussionmentioning

confidence: 99%

Post-acute Sequelae of SARS-CoV-2 Infection: A Neglected Public Health Issue

Wang

Yang

2022

Front. Public Health

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Section: Discussionmentioning

confidence: 99%

Post-acute Sequelae of SARS-CoV-2 Infection: A Neglected Public Health Issue

Wang

Yang

2022

Front. Public Health

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“…Recent studies demonstrated a direct and indirect antiviral effect of GR and BA against SARS-CoV-2 which supports the rationale for the use of GR and BA for the treatment of COVID-19. Yi et al ( 2021 ) found that GR and triterpenoids from licorice effectively inhibit SARS-CoV-2 infection by affecting virus entry and replication. This study provides important experimental evidence for the clinical efficacy of GR in our clinical study.…”

Section: Discussionmentioning

confidence: 99%

Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial

et al. 2022

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Recent evidence points to a potential therapeutic role for glycyrrhizin(GR) and boswellic acids (BA) in the treatment of COVID-19 but conclusive evidence is lacking. Our aim is to investigate the efficacy of GR + BA versus placebo for the treatment of hospitalized patients with moderate SARS-CoV-2 or COVID-19 variants infection. The current study is a randomized, double-blind, placebo-controlled, single-center trial. Patients with SARS-CoV-2 or COVID-19 variants diagnosed by PCR test who were admitted to Sohag University hospital were eligible if they were at least 18 years of age and had moderate symptoms. Patients were randomly assigned to receive oral GR capsule (60 mg) and BA (200 mg) twice daily for 14 days or a matching placebo. All patients also received treatment with the institutional protocol for COVID-19. The primary outcome was mortality and time to recovery. Secondary outcome was clinical status score, 14 days after receiving study drugs. Adverse events from use of study drugs have been evaluated for up to 14 days. The trial is registered at ClinicalTrials.gov (Identifier NCT04487964). During the 6-month enrollment period (June-November, 2021) only 50 patients (54% women; median age 60 years, IQR 54–65) met eligibility and were randomly assigned. Evaluation of the primary outcome at 14 days showed that there were five deaths in the placebo group and no deaths in the GR + BA group. With regard to recovery time, it was significantly shorter (p = 0.0001) in the group receiving GR + BA capsule compared to the placebo group (median 7.0; IQR 6.0–8.0 days vs. median 12.5; IQR 12–20 days). Clinical status on the ordinal score scale as a secondary outcome showed a significant difference between the GR + BA group (median (IQR) score, 2 [2–3]) and placebo groups (mean (IQR) score, 3 [3–5.5]). There was a significant decrease in CRB (p = 0.000041) in GR + BA compared with the placebo group. In conclusion, this safe, inexpensive, antiviral, immunomodulating and anti-inflammatory combination may be considered for use in mild to moderate infections of SARS-CoV-2 or COVID-19 variants. The study is limited by the small sample size; therefore, larger randomized trials are required.

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“…Soyasaponin and other saponins are known to possess in vitro antiviral activity against herpes simplex virus type 1, human cytomegalovirus, influenza virus and human immunodeficiency virus type 1 [ 43 , 44 ]. Licorice-saponin A3 and Esculeoside A, a type of saponin, have been demonstrated to bind to SARS-CoV-2 RBD and have antiviral activity [ 45 , 46 ]. In the current study, the docking simulation and binding assay showed that Soyasaponin I bound to the RBD with relatively low affinity as compared with a previously reported inhibitor [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the current study, the docking simulation and binding assay showed that Soyasaponin I bound to the RBD with relatively low affinity as compared with a previously reported inhibitor [ 47 ]. Licorice-saponin A3 suppresses SARS-CoV-2 infection by not only inhibiting RBD–ACE2 interaction but also inhibiting non-structural protein 7 [ 45 ]. Soyasaponin I induces macroautophagy by inhibiting the Akt signaling pathway [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization and Utilization of Disulfide-Bonded SARS-CoV-2 Receptor Binding Domain of Spike Protein Synthesized by Wheat Germ Cell-Free Production System

Yamaoka

Jeremiah

Funabashi

et al. 2022

Viruses

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The spike protein (SP) of SARS-CoV-2 is an important target for COVID-19 therapeutics and vaccines as it binds to the ACE2 receptor and enables viral infection. Rapid production and functional characterization of properly folded SP is of the utmost importance for studying the immunogenicity and receptor-binding activity of this protein considering the emergence of highly infectious viral variants. In this study, we attempted to express the receptor-binding region (RBD) of SARS-CoV-2 SP containing disulfide bonds using the wheat germ cell-free protein synthesis system. By adding protein disulfide isomerase (PDI) and endoplasmic reticulum oxidase (ERO1α) to the translational reaction mixture, we succeeded in synthesizing a functionally intact RBD protein that can interact with ACE2. Using this RBD protein, we have developed a high-throughput AlphaScreen assay to evaluate the RBD–ACE2 interaction, which can be applied for drug screening and mutation analysis. Thus, our method sheds new light on the structural and functional properties of SARS-CoV-2 SP and has the potential to contribute to the development of new COVID-19 therapeutics.

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Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection

Cited by 68 publications

References 39 publications

Post-acute Sequelae of SARS-CoV-2 Infection: A Neglected Public Health Issue

Post-acute Sequelae of SARS-CoV-2 Infection: A Neglected Public Health Issue

Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial

Characterization and Utilization of Disulfide-Bonded SARS-CoV-2 Receptor Binding Domain of Spike Protein Synthesized by Wheat Germ Cell-Free Production System

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