Discovery of Potent Dengue Virus NS2B-NS3 Protease Inhibitors Among Glycyrrhizic Acid Conjugates with Amino Acids and Dipeptides Esters.

This study investigated a library of known and novel glycyrrhizic acid (GL) conjugates with amino acids and dipeptide esters, as inhibitors of the DENV NS2B-NS3 protease. We utilized docking algorithms to evaluate the interactions of these GL derivatives with key residues (His51, Asp75, Ser135, and Gly153) within 10 Å of the DENV-2 NS2B-NS3 protease binding pocket (PDB ID: 2FOM). It was found that compounds and exhibited unique binding patterns, forming hydrogen bonds with Asp75, Tyr150, and Gly153.

Glycyrrhizic acid conjugates with amino acid methyl esters target the main protease, exhibiting antiviral activity against wild-type and nirmatrelvir-resistant SARS-CoV-2 variants.

COVID-19 pandemic is predominantly caused by SARS-CoV-2, with its main protease, Mpro, playing a pivotal role in viral replication and serving as a potential target for inhibiting different variants. In this study, potent Mpro inhibitors were identified from glycyrrhizic acid (GL) derivatives with amino acid methyl/ethyl esters. Out of the 17 derivatives semisynthesized, Compounds 2, 6, 9, and 15, with methionine methyl esters, D-tyrosine methyl esters, glutamic acid methyl esters, and methionines in the carbohydrate moiety, respectively, significantly inhibited wild-type SARS-CoV-2 Mpro-mediated proteolysis, with IC50 values ranging from 0.

Synthesis, modification and biological activity of 2,3-indoles of Glycyrrhetinic acid.

The synthesis of 2,3-indoles of Glycyrrhetinic acid (GLA) and its methyl ester was carried out by the Fischer reaction. Reductive transformations of GLA methyl ester 2,3-indole were carried out to obtain 11-deoxo- and 9,12-diene analogs. N-methylation of 2,3-indole gave N-methyl-indole-11-oxo-18β-olean-12-en-30-oic acid.

Synthesis of Glycyrrhizic Acid Conjugates with Amino-Acid Methyl Esters and their Ability to Stimulate Antibody Genesis in Mice.

Conjugates of glycyrrhizic acid (GA) with methyl esters of -amino acids (valine, methionine, and glutamic acid) containing the amino-acid residues in the carbohydrate moiety of the glycoside were synthesized using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The resulting GA conjugates at a dose of 2 mg/kg stimulated a primary immune response (production of antibody-forming cells, AFCs) in outbred mice by 1.6 - 3 times as compared with the control.

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

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.