Microbicide Containing Ellagic Acid Can Inhibit HIV-1 Infection

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-11, Vol.27 (22), p.7941
• Main Authors: Nittayananta, Wipawee, Promsong, Aornrutai, Levy, Claire, Hladik, Florian, Chaitaveep, Nithinart, Ungphaiboon, Suwipa, Tewtrakul, Supinya, Satthakarn, Surada
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - pharmacology; Antiviral activity; Antiviral agents; Biological effects; CCR5 protein; CD4 antigen; Cell culture; chemokines; Cytokines; Cytokines - pharmacology; Cytotoxicity; Drug dosages; Drug resistance; Ellagic acid; Ellagic Acid - pharmacology; Enzymatic activity; Enzyme activity; Enzymes; Female; Flavonoids; Glycoproteins; Health aspects; Herbal medicine; HIV; HIV (Viruses); HIV infection; HIV Infections - drug therapy; HIV-1; Human immunodeficiency virus; Humans; Immunology; Infections; Integrase; Lymphocytes; Medical research; Medicine, Experimental; microbicide gel; Molybdenum alloys; Proteases; Replication
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27227941

Ellagic acid (EA) has a wide range of biological effects. The purpose of this study was to investigate the in vitro effects of EA on HIV-1 replication, viral enzyme activity and cytokine secretion by infected cells. The anti-HIV-1 activity of EA in solution was determined in vitro using the infection of TZM-bl cells by the nano luciferase-secreting R5-tropic JRCSF strain of HIV-1, which allows for the quantification of viral growth by measuring nano luciferase in the culture supernatants. The effect of EA on the cytokine secretion of TZM-bl cells was determined by a multiplexed bead array after 48 h of HIV-1 exposure. The antiviral effect of EA in the gel formulation (Ellagel), as would be used for vaginal application, was investigated by the inhibition of infection of UC87.CD4.CCR5 cells with R5-tropic pBaLEnv-recombinant HIV-1. EA in solutions of up to 100 µM was not toxic to TZM-bl cells. EA added either 1 h before or 4 h after HIV-1 exposure suppressed the replication of R5-tropic HIV-1 in TZM-bl cells in a dose-dependent manner, with up to 69% inhibition at 50 µM. EA-containing solutions also exhibited a dose-dependent inhibitory effect on HIV-1 replication in U87 cells. When EA was formulated as a gel, Ellagel containing 25 µM and 50 µM EA inhibited HIV-1 replication in U87 cells by 56% and 84%, respectively. In assays of specific HIV-1 enzyme activity, Ellagel inhibited HIV-1 integrase but not protease. EA did not significantly modulate cytokine secretion. We conclude that EA either in solution or in a gel form inhibits HIV infection without adverse effects on target cells. Thus, gel containing EA can be tested as a new microbicide against HIV infection.