Glycyrrhetinic acid derivatives as Zika virus inhibitors: Synthesis and antiviral activity in vitro

Baltina, L. A.; Lai, Hsueh‐Chou; Liu, Ya-Chi; Huang, Su-Hua; Hour, Mann‐Jen; Балтина, Л. А.; Nugumanov, T. R.; Borisevich, Sophia S.; Халилов, Л. М.; Петрова, С. Ф.; Khursan, S. L.; Lin, Cheng‐Wen

doi:10.1016/j.bmc.2021.116204

Cited by 30 publications

(22 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…( G. inflata ) are the basic liquorice plants listed in the Chinese Pharmacopoeia 27 . Their roots and rhizomes have various pharmacological activities, such as anti-tumour 28 , anti-viral 29 , and anti-inflammatory 30 effects. Furthermore, liquorice plants survive in extreme environments, such as those characterised by low temperature, drought, and high salinity and alkalinity.…”

Section: Introductionmentioning

confidence: 99%

Silicon improves ion homeostasis and growth of liquorice under salt stress by reducing plant Na+ uptake

Shen

Wang

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Silicon (Si) effectively alleviates the effects of salt stress in plants and can enhance salt tolerance in liquorice. However, the mechanisms by which Si improved salt tolerance in liquorice and the effects of foliar application of Si on different liquorice species under salt stress are not fully understood. We investigated the effects of foliar application of Si on the growth, physiological and biochemical characteristics, and ion balance of two liquorice species, Glycyrrhiza uralensis and G. inflata. High salt stress resulted in the accumulation of a large amount of Na+, decreased photosynthetic pigment concentrations, perturbed ion homeostasis, and eventually inhibited both liquorice species growth. These effects were more pronounced in G. uralensis, as G. inflata is more salt tolerant than G. uralensis. Foliar application of Si effectively reduced the decomposition of photosynthetic pigments and improved gas exchange parameters, thereby promoting photosynthesis. It also effectively inhibited lipid peroxidation and leaf electrolyte leakage and enhanced osmotic adjustment of the plants. Furthermore, Si application increased the K+ concentration and reduced Na+ absorption, transport, and accumulation in the plants. The protective effects of Si were more pronounced in G. uralensis than in G. inflata. In conclusion, Si reduces Na+ absorption, improves ion balance, and alleviates the negative effects of salt stress in the two liquorice species studied, but the effect is species dependent. These findings may help to develop novel strategies for protecting liquorice plants against salt stress and provide a theoretical basis for the evaluation of salt tolerance and the scientific cultivation of liquorice.

show abstract

Section: Introductionmentioning

confidence: 99%

Silicon improves ion homeostasis and growth of liquorice under salt stress by reducing plant Na+ uptake

Shen

Wang

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…DENV-1 isolate CMUH 2018-4 and DENV-2 strain 16681 used in this study were propagated in monkey kidney epithelial Vero E6 cells (Bioresource Collection and Research Center (BCRC), Hsinchu, Taiwan). The cultured media of infected Vero E6 cells were harvested 5 days post-infection, and virus titer of the stock was determined using the mean (50%) tissue culture infectious dose (TCID50) per mL [ 45 , 59 , 60 ]. Vero E6 cells and human lung epithelial A549 cells (BCRC, Hsinchu, Taiwan) that were cultured in DMEM supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin, were used to explore antiviral potential and the mechanisms of GL conjugates with methyl or ethyl esters of L- and D-amino acids (Compounds 2 – 21 ) against DENV1 and DENV2.…”

Section: Methodsmentioning

confidence: 99%

“…In the antiviral screening assay, each tested GL conjugate at 10 μM was used to survey the anti-DENV activity in Vero E6 cells using cytopathic effect (CPE) and infectivity reduction assays as described in our prior report [ 45 , 59 , 60 ]. In CPE and infectivity reduction assays, Vero E6 cells were infected by DENV2 at an MOI of 0.005 and simultaneously treated 10 μM of indicated GL conjugate for 96 h, and then photographed by microscope for examining the levels of DENV2-induced CPE in infected cells treated with or without GL conjugate.…”

Section: Methodsmentioning

confidence: 99%

Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity

Hour

Chen

Lin

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Dengue virus (DENV) is one of the most geographically distributed mosquito-borne flaviviruses, like Japanese encephalitis virus (JEV), and Zika virus (ZIKV). In this study, a library of the known and novel Glycyrrhizic acid (GL) derivatives bearing amino acid residues or their methyl/ethyl esters in the carbohydrate part were synthesized and studied as DENV inhibitors in vitro using the cytopathic effect (CPE), viral infectivity and virus yield assays with DENV1 and DENV-2 in Vero E6 and A549 cells. Among the GL conjugates tested, compound hits GL-D-ValOMe 3, GL-TyrOMe 6, GL-PheOEt 11, and GL-LysOMe 21 were discovered to have better antiviral activity than GL, with IC50 values ranging from <0.1 to 5.98 μM on the in vitro infectivity of DENV1 and DENV2 in Vero E6 and A549 cells. Compound hits 3, 6, 11, and 21 had a concentration-dependent inhibition on the virus yield in Vero E6, in which GL-D-ValOMe 3 and GL-PheOEt 11 were the most active inhibitors of DENV2 yield. Meanwhile, the time-of-addition assay indicated that conjugates GL-D-ValOMe 3 and GL-PheOEt 11 exhibited a substantial decrease in the DENV2 attachment stage. Subsequently, chimeric single-round infectious particles (SRIPs) of DENV2 C-prM-E protein/JEV replicon and DENV2 prM-E/ZIKV replicon were utilized for the DENV envelope I protein-mediated attachment assay. GL conjugates 3 and 11 significantly reduced the attachment of chimeric DENV2 C-prM-E/JEV and DENV2 prM-E/ZIKV SRIPs onto Vero E6 cells in a concentration-dependent manner but did not impede the attachment of wild-type JEV CprME/JEV and ZIKV prM-E/ZIKV SRIPs, indicating the inhibition of Compounds 3 and 11 on DENV2 E-mediated attachment. Molecular docking data revealed that Compounds 3 and 11 have hydrophobic interactions within a hydrophobic pocket among the interfaces of Domains I, II, and the stem region of the DENV2 envelope (E) protein. These results displayed that Compounds 3 and 11 were the lead compounds targeting the DENV E protein. Altogether, our findings provide new insights into the structure–activity relationship of GL derivatives conjugated with amino acid residues and can be the new fundamental basis for the search and development of novel flavivirus inhibitors based on natural compounds.

show abstract

“…Unlike the parent compound glycyrrhizic acid that exerts anti-DENV-2 activity (IC 50 8.1 µM), its derivatization through chemical conjugation with isoleucine and 11-aminoundecanoic acid methyl ester resulted in potent compounds 73 (IC 50 1.3 µM) and 74 (IC 50 1.2 µM) [ 142 ]. Through a similar strategy, a more recent study reported derivatives of a pentacyclic triterpenoid, glycyrrhetinic acid from G. gabra , with potent anti-ZIKV replication activity [ 143 ]. The resultant compounds 75 – 78 had IC 50 values of 0.13 µM, 0.55 µM, 0.29 µM and 0.56 µM, respectively.…”

Section: Transmission-blocking In Pursuit Of Human Disease Eliminatio...mentioning

confidence: 99%

Contemporary exploitation of natural products for arthropod-borne pathogen transmission-blocking interventions

et al. 2022

View full text Add to dashboard Cite

An integrated approach to innovatively counter the transmission of various arthropod-borne diseases to humans would benefit from strategies that sustainably limit onward passage of infective life cycle stages of pathogens and parasites to the insect vectors and vice versa. Aiming to accelerate the impetus towards a disease-free world amid the challenges posed by climate change, discovery, mindful exploitation and integration of active natural products in design of pathogen transmission-blocking interventions is of high priority. Herein, we provide a review of natural compounds endowed with blockade potential against transmissible forms of human pathogens reported in the last 2 decades from 2000 to 2021. Finally, we propose various translational strategies that can exploit these pathogen transmission-blocking natural products into design of novel and sustainable disease control interventions. In summary, tapping these compounds will potentially aid in integrated combat mission to reduce disease transmission trends.

show abstract

Glycyrrhetinic acid derivatives as Zika virus inhibitors: Synthesis and antiviral activity in vitro

Cited by 30 publications

References 38 publications

Silicon improves ion homeostasis and growth of liquorice under salt stress by reducing plant Na+ uptake

Silicon improves ion homeostasis and growth of liquorice under salt stress by reducing plant Na+ uptake

Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity

Contemporary exploitation of natural products for arthropod-borne pathogen transmission-blocking interventions

Contact Info

Product

Resources

About