Glycyrrhizic acid exerts inhibitory activity against the spike protein of SARS-CoV-2

Abstract

Coronavirus causes a disease with high infectivity and pathogenicity, especially SARS in 2003, MERS in 2012, and COVID-2019 currently. The spike proteins of these coronaviruses are critical for host cell entry by receptors. Thus, searching for broad-spectrum anti-coronavirus candidates, such as spike protein inhibitors, is vital and desirable due to the mutations in the spike protein. In this study, a combination of computer-aided drug design and biological verification was used to discover active monomers from traditional Chinese medicine. Surface plasmon resonance (SPR) assays and NanoBit assays were used to verify the predicated compounds with their binding activities to spike proteins and inhibitory activities on the SARS-CoV-2 RBD/ACE2 interaction, respectively. Furthermore, an MTT assay was used to evaluate the cell toxicities of active compounds. As a result, glycyrrhizic acid ( ZZY-44 ) was found to be the most efficient and nontoxic broad-spectrum anti-coronavirus molecule in vitro , especially, the significant effect on SARS-CoV-2, which provided a theoretical basis for the study of the pharmacodynamic material basis of traditional Chinese medicine against SARS-CoV-2 and offered a lead compound for further structural modification in order to obtain more effective candidate drugs against SARS-CoV-2.

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

“…Chemical components of the Lianhuaqingwen capsule, a commonly used antiviral TCM containing neochlorogenic acid, amygdalin, prunasin, forsythoside I, rutin, forsythoside A, and rhein, exhibited binding affinities to ACE2 with K D values ranging from 0.2 to 82.4 μmol/L, interrupted SARS-CoV-2 spike protein binding to ACE2 with different efficacies ( X. Chen et al, 2020 ), inhibited SARS-CoV-2 replication in Vero-E6 cells and reduced pro-inflammatory cytokine expression in Huh-7 cells ( Runfeng et al, 2020 ). Glycyrrhizin and its derivatives, active components of liquorice roots used in TCM, bind to ACE2 (K D of 4.4.μmol/L) and inhibit the interaction of SARS-CoV-2 spike protein with ACE2 (S. Yu et al, 2020 ). They also decrease the replication of SARS-CoV ( Hoever et al, 2005 ) and SARS-CoV-2 in cell lines ( X. Chen et al, 2020 ; S. Yu et al, 2020 ).…”

“…Glycyrrhizin and its derivatives, active components of liquorice roots used in TCM, bind to ACE2 (K D of 4.4.μmol/L) and inhibit the interaction of SARS-CoV-2 spike protein with ACE2 (S. Yu et al, 2020 ). They also decrease the replication of SARS-CoV ( Hoever et al, 2005 ) and SARS-CoV-2 in cell lines ( X. Chen et al, 2020 ; S. Yu et al, 2020 ). Baicalin , a flavonoid isolated from the roots of Scutellaria baicalensis Georgi (Huang Qin) used in TCM, has anti-oxidative, anti-viral, anti-inflammatory, anti-HIV and anti-proliferative activities.…”

Can Antiviral Activity of Licorice Help Fight COVID-19 Infection?

“…Several in silico docking studies suggested a direct interaction of GR and GA to these key players in virus internalization and replication: ACE2 [61][62][63], spike protein and its RBD [63][64][65][66], and 3CLPro [63,65,[67][68][69][70][71][72][73][74]. Only a few in silico analyses were negative (3CLpro [68,75], Spike [76]).…”

pH-Sensitive Glycyrrhizin Based Vesicles for Nifedipine Delivery

“…It is widely investigated from the point of its biological activity: hepatoprotective, antiviral (including recently discovered activity against SARS-CoV-2), anticancer, etc. [ 9 , 10 , 11 , 12 , 13 ]. GA also demonstrates the ability to enhance the activity of other drugs [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”