The review is devoted to the problem of creating new antiviral drugs based on glycyrrhizic acid (GA), the major triterpene glycoside extracted from roots of common and Ural licorice (Glycyrrhiza glabra L. and G. uralensis Fisher, respectively). Published data on the natural GA sources, antiviral activity of GA and its derivatives, clinical applications of GA-based drugs, and the properties of GA-containing biologically active nutrient additives are summarized. Possible mechanisms of the antiviral activity of GA and its derivatives are examined. It is shown that chemical modification of GA is a promising way of designing new highly active antiviral drugs for the prophylaxis and treatment of HIV, hepatitis B and C, corona-virus, and herpes simplex virus infections.

New glycyrrhizic acid (GA) conjugates were synthesized with the use of tert-butyl esters of amino acids or benzyl esters of dipeptides; they contained two residues of L-amino acids (Met, Phe, Pro, and Ile or dipeptides Gly-Leu and Gly-Phe). Activation of GA carboxy groups was carried out with the help of N-hydroxysuccinimide, N,N'-dicyclohexylcarbodiimide, or N-hydroxybenzotriazole with dicyclohexylcarbodiimide. A proline-containing GA derivative is a low-toxic substance; it raises the level of agglutinins by 3.7 times in the blood of mice and 3 times that of hemolysins compared with the control. Dipeptide GA derivatives possess an expressed anti-HIV-1 activity in cultures of MT-4 cells and are 90-70 times less cytotoxic than azidothymidine. The selectivity index of the compounds exceeds those of GA by 110 and 34 times, respectively.

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Activated esters and N-hydroxybenzotriazole-N,N′-dicyclohexylcarbodiimide (DCC) or N-hydroxysuccinimide-DCC were used to synthesize conjugates of glycyrrhizic acid (GA) with N ε -carbobenzyloxy-Llysine [Lys(Z)-OH] and its esters containing two or three amino components. It was shown that the conjugate of GA 30-methyl ester with Lys(Z)-OH possessed anti-HIV-1 activity.

New conjugates of 18E-and 18D-glycyrrhizic acids (GAs) each containing two di-or D-methyl esters of L-aspartic acid in the carbohydrate part of the glycosides were synthesized by the activated ester method using the N-hydroxysuccinimide (HOSu) and N,Nc-dicyclohexylcarbodiimide. It was found that the conjugate of 18E-GA with Asp(OMe)(OMe) (4) at a concentration of 250 Pg/mL inhibited effectively RT of HIV-1 and the accumulation of virus antigen p24 in MT-4 cell culture (95-97%) and protected cells from the cytopathogenic action of the virus.The search for novel immunostimulators and antiviral agents with a new mechanism of action among natural compounds obtained from renewable plant resources and their modified forms is a burgeoning area of modern bioorganic and medicinal chemistry. This is explained by the broad distribution of HIV-infections, viral hepatitises B and C, and the emergence of new viral respiratory infections.