Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome?
Identifieur interne : 001291 ( Main/Corpus ); précédent : 001290; suivant : 001292Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome?
Auteurs : Christian Bailly ; Gérard VergotenSource :
- Pharmacology & therapeutics [ 1879-016X ] ; 2020.
English descriptors
- KwdEn :
- Alarmins (drug effects), Betacoronavirus (MeSH), COVID-19 (MeSH), Coronavirus Infections (drug therapy), Coronavirus Infections (epidemiology), Drug Therapy, Combination (MeSH), Glycyrrhizic Acid (pharmacology), Glycyrrhizic Acid (therapeutic use), Humans (MeSH), Hydroxychloroquine (therapeutic use), Membrane Microdomains (drug effects), Molecular Docking Simulation (MeSH), Pandemics (MeSH), Pneumonia, Viral (drug therapy), Pneumonia, Viral (epidemiology), SARS-CoV-2 (MeSH), Tenofovir (therapeutic use).
- MESH :
- chemical , drug effects : Alarmins.
- drug effects : Membrane Microdomains.
- drug therapy : Coronavirus Infections, Pneumonia, Viral.
- epidemiology : Coronavirus Infections, Pneumonia, Viral.
- chemical , pharmacology : Glycyrrhizic Acid.
- chemical , therapeutic use : Glycyrrhizic Acid, Hydroxychloroquine, Tenofovir.
- Betacoronavirus, COVID-19, Drug Therapy, Combination, Humans, Molecular Docking Simulation, Pandemics, SARS-CoV-2.
Abstract
Safe and efficient drugs to combat the current COVID-19 pandemic are urgently needed. In this context, we have analyzed the anti-coronavirus potential of the natural product glycyrrhizic acid (GLR), a drug used to treat liver diseases (including viral hepatitis) and specific cutaneous inflammation (such as atopic dermatitis) in some countries. The properties of GLR and its primary active metabolite glycyrrhetinic acid are presented and discussed. GLR has shown activities against different viruses, including SARS-associated Human and animal coronaviruses. GLR is a non-hemolytic saponin and a potent immuno-active anti-inflammatory agent which displays both cytoplasmic and membrane effects. At the membrane level, GLR induces cholesterol-dependent disorganization of lipid rafts which are important for the entry of coronavirus into cells. At the intracellular and circulating levels, GLR can trap the high mobility group box 1 protein and thus blocks the alarmin functions of HMGB1. We used molecular docking to characterize further and discuss both the cholesterol- and HMG box-binding functions of GLR. The membrane and cytoplasmic effects of GLR, coupled with its long-established medical use as a relatively safe drug, make GLR a good candidate to be tested against the SARS-CoV-2 coronavirus, alone and in combination with other drugs. The rational supporting combinations with (hydroxy)chloroquine and tenofovir (two drugs active against SARS-CoV-2) is also discussed. Based on this analysis, we conclude that GLR should be further considered and rapidly evaluated for the treatment of patients with COVID-19.
DOI: 10.1016/j.pharmthera.2020.107618
PubMed: 32592716
PubMed Central: PMC7311916
Links to Exploration step
pubmed:32592716Le document en format XML
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<term>Coronavirus Infections (drug therapy)</term>
<term>Coronavirus Infections (epidemiology)</term>
<term>Drug Therapy, Combination (MeSH)</term>
<term>Glycyrrhizic Acid (pharmacology)</term>
<term>Glycyrrhizic Acid (therapeutic use)</term>
<term>Humans (MeSH)</term>
<term>Hydroxychloroquine (therapeutic use)</term>
<term>Membrane Microdomains (drug effects)</term>
<term>Molecular Docking Simulation (MeSH)</term>
<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (drug therapy)</term>
<term>Pneumonia, Viral (epidemiology)</term>
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<front><div type="abstract" xml:lang="en">Safe and efficient drugs to combat the current COVID-19 pandemic are urgently needed. In this context, we have analyzed the anti-coronavirus potential of the natural product glycyrrhizic acid (GLR), a drug used to treat liver diseases (including viral hepatitis) and specific cutaneous inflammation (such as atopic dermatitis) in some countries. The properties of GLR and its primary active metabolite glycyrrhetinic acid are presented and discussed. GLR has shown activities against different viruses, including SARS-associated Human and animal coronaviruses. GLR is a non-hemolytic saponin and a potent immuno-active anti-inflammatory agent which displays both cytoplasmic and membrane effects. At the membrane level, GLR induces cholesterol-dependent disorganization of lipid rafts which are important for the entry of coronavirus into cells. At the intracellular and circulating levels, GLR can trap the high mobility group box 1 protein and thus blocks the alarmin functions of HMGB1. We used molecular docking to characterize further and discuss both the cholesterol- and HMG box-binding functions of GLR. The membrane and cytoplasmic effects of GLR, coupled with its long-established medical use as a relatively safe drug, make GLR a good candidate to be tested against the SARS-CoV-2 coronavirus, alone and in combination with other drugs. The rational supporting combinations with (hydroxy)chloroquine and tenofovir (two drugs active against SARS-CoV-2) is also discussed. Based on this analysis, we conclude that GLR should be further considered and rapidly evaluated for the treatment of patients with COVID-19.</div>
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<ArticleTitle>Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome?</ArticleTitle>
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<Abstract><AbstractText>Safe and efficient drugs to combat the current COVID-19 pandemic are urgently needed. In this context, we have analyzed the anti-coronavirus potential of the natural product glycyrrhizic acid (GLR), a drug used to treat liver diseases (including viral hepatitis) and specific cutaneous inflammation (such as atopic dermatitis) in some countries. The properties of GLR and its primary active metabolite glycyrrhetinic acid are presented and discussed. GLR has shown activities against different viruses, including SARS-associated Human and animal coronaviruses. GLR is a non-hemolytic saponin and a potent immuno-active anti-inflammatory agent which displays both cytoplasmic and membrane effects. At the membrane level, GLR induces cholesterol-dependent disorganization of lipid rafts which are important for the entry of coronavirus into cells. At the intracellular and circulating levels, GLR can trap the high mobility group box 1 protein and thus blocks the alarmin functions of HMGB1. We used molecular docking to characterize further and discuss both the cholesterol- and HMG box-binding functions of GLR. The membrane and cytoplasmic effects of GLR, coupled with its long-established medical use as a relatively safe drug, make GLR a good candidate to be tested against the SARS-CoV-2 coronavirus, alone and in combination with other drugs. The rational supporting combinations with (hydroxy)chloroquine and tenofovir (two drugs active against SARS-CoV-2) is also discussed. Based on this analysis, we conclude that GLR should be further considered and rapidly evaluated for the treatment of patients with COVID-19.</AbstractText>
<CopyrightInformation>Copyright © 2020 Elsevier Inc. All rights reserved.</CopyrightInformation>
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<CoiStatement>Declaration of Competing Interest The authors declare no conflict of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.</CoiStatement>
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