[The anti-HIV activity of glycyrrhizic acid penta-O-nicotinate].

The anti-HIV activity of niglizin (penta-O-nicotinate of glycyrrhizic acid) and of its combinations was studied in the culture of infected MT-4 cells and in respect to the recombinant reverse HIV-1 transcriptase. Niglizin was shown to suppress effectively the HIV replication and to be a noncompetitive inhibitor of reverse transcriptase. Research of a combined anti-HIV action of niglizin and of azidothimidine (AZT) demonstrated that the preparations, when used at ratios of 1:20, 1:50, 1:200 and 1:2000, suppressed the synergetic effect both in the cell culture and in the recombinant reverse HIV transcriptase.

[New phosphonoformic acid derivatives of 3'-azido-3'-deoxythymidine].

New 5'-alkyl ethoxy- and aminocarbonylphosphonates of 3'-azido-3'-deoxythymidine (AZT) were synthesized, and their antiviral properties in HIV-1-infected cell cultures and stability to chemical hydrolysis were studied. The AZT 5'-aminocarbonylphosphonates were shown to be significantly more stable in phosphate buffer (pH 7.2) than the corresponding ethoxycarbonylphosphonates.

[Determination of glycyrrhizic acid binding sites by a phage display method].

Phages that expose peptides specifically interacting with glycyrrhizic acid (GA) were selected from a phage peptide library by affinity selection and ELISA. Amino acid sequence analysis of the selected peptides and human proteins with the SIM program revealed homology to tyrosine protein kinases, serine/threonine protein kinases, tyrosine phosphatases, and some receptors. Analysis of the peptide and virus protein sequences with the BLAST program showed that GA has affinity for various surface proteins of several human viruses such as HIV-1, hepatitis C virus, and herpesviruses.

[Chronically HIV-1 infected human monocyte culture U937 as a model for assessing the efficacy of anti-HIV agents].

Cell culture U937 chronically infected with HIV-1 is suggested as a model for adequate evaluation of antiviral activity of HIV inhibitors. Azidothimidine (AZT) notable decreased HIV-1 reproduction in chronically infected U937 cells to passages 15-18. Glycirrhizic acid (GA) effectively inhibited the virus production during the first four passages, while in subsequent passages (up to passage 20) decreased the virus production by only 60% in comparison with the control.

[Immunoenzyme test-system for detection of glycyrrhizic acid].

An experimental enzyme immunoassay test kit was developed for detecting glycyrrhizic acid (GA) during pharmacokinetic investigations. This method was used to determine the GA content in the blood plasma of mice and guinea pigs after intraperitoneal and intravenous injections. The results of the GA determination using the new test kit agree with the data obtained by HPLC.

[Immunochemical homology of HIV-1 envelope proteins and human apolipoprotein AI].

Immunochemical homology of envelope HIV proteins and human apolipoprotein A-I was for the first time detected by ELISA. Immunochemical reactions between antibodies to apoA-I and HIV envelope proteins and between apoA-I and anti-HIV antibodies present in the blood of AIDS patients were shown. These data suggest that the homology of surface HIV proteins and human apoA-I can lead to competitive relationships impeding the involvement of human apoA-I in gene expression regulation.

[Isolation of a panel of HIV-positive serum by blocking them with various HIV antigens].

A new methodological approach to preparation of a panel of positive sera containing antibodies to individual viral proteins has been developed. The method consists in exhaustion of initial sera from HIV-infected patients with the known titers of antibodies by HIV antigens differing by the spectrum of virus proteins. Antigen preparations containing the least amounts of envelope proteins were selected for exhaustion.

[Detection of human immunodeficiency virus (HIV-1) p24 antigen in immune complexes].

Enzyme-linked immunosorbent assay (ELISA) test-system for HIV-1 p24 antigen detection in human blood specimens has been developed. Use of complex biotin-streptavidin-horseradish peroxidase conjugate increased the sensitivity of the method to 50 pg/ml. The test system is characterized by 100 percent specificity, whereas direct p24 assay detects the antigen in only 5 percent of 100 sera of HIV-infected patients, since even low-titer sera efficiently mask p24.

[The anti-HIV activity of beta-glycyrrhizic acid].

The anti-HIV activity of beta-glycyrrhizic acid (GA) and various derivatives was studied using various strains of HIV-1 and HIV-2 in primary infected lymphoblastoid cells MT-4 and monocyte cell line U-973 chronically infected with HIV-1 and containing provirus (GKV 4005). Beta-glycyrrhizic acid and its derivatives were shown to effectively inhibit HIV-1 reproduction in MT-4 cells. The antiviral effect of beta-GA sodium salt exceeded that of AZT in cells GKV 4005.

[The detection and quantitative determination of antigens to the human immunodeficiency virus types 1 and 2].

Three modifications of ELISA test system for HIV antigen detection are described. They are based on IgG from HIV-1 and HIV-2-infected human sera and monoclonal antibodies against HIV-1 p24 used as immunosorbents. The peroxidase/anti-HIV-IgG conjugate was used in all the test systems.

[Study of antigenic structure of HIV-1 protein p24 using monoclonal antibodies].

During the experiments 4 murine and 3 rat hybridomas producing monoclonal antibodies (MAb) against the protein p24 of human immunodeficiency virus type 1 (HIV-1) have been obtained. Using the immunoblotting technique, it was established that all the species of MAb reacted with the same viral proteins which are derivatives of gag gene--p24 and p55. The properties of MAb have been studied in competitive binding.