Hydroxytyrosol

Abstract

Objective:To investigate the toxicity and activity against HIV of 5-hydroxytyrosol as a potential microbicide.Design:The anti-HIV-1 activity of 5-hydroxytyrosol, a polyphenolic compound, was tested against wild-type HIV-1 and viral clones resistant to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors and integrase inhibitors. In addition to its activity against founder viruses, different viral subtypes and potential synergy with tenofovir disoproxil fumarate, lamivudine and emtricitabine was also tested. 5-Hydroxytyrosol toxicity was evaluated in vivo in rabbit vaginal mucosa.Methods:We have cloned pol gene from drug-resistant HIV-1 isolated from infected patients and env gene from Fiebeg III/IV patients or A, C, D, E, F and G subtypes in the NL4.3-Ren backbone. 5-Hydroxytyrosol anti-HIV-1 activity was evaluated in infections of MT-2, U87-CCR5 or peripheral blood mononuclear cells preactivated with phytohemagglutinin + interleukin-2 with viruses obtained through 293T transfections. Inhibitory concentration 50% and cytotoxic concentration 50% were calculated. Synergy was analysed according to Chou and Talalay method. In-vivo toxicity was evaluated for 14 days in rabbit vaginal mucosa.Results:5-Hydroxytyrosol inhibited HIV-1 infections of recombinant or wild-type viruses in all the target cells tested. Moreover, 5-hydroxytyrosol showed similar inhibitory concentration 50% values for infections with NRTIs, NNRTIs, protease inhibitors and INIs resistant viruses; founder viruses and all the subtypes tested. Combination of 5-hydroxytyrosol with tenofovir was found to be synergistic, whereas it was additive with lamivudine and emtricitabine. In-vivo toxicity of 5-hydroxytyrosol was very low even at the highest tested doses.Conclusion:5-Hydroxytyrosol displayed a broad anti-HIV-1 activity in different cells systems in the absent of in-vivo toxicity, therefore supporting its candidacy as a potential new class of microbicides.

Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health

“…HTyr was identified as a unique class of HIV-1 inhibitors that prevent HIV from entering into the host cell and binding the catalytic site of the HIV-1, with both, viral entry and integration inhibited [91]. Furthermore, it was reported that HTyr inactivated influenza A viruses, suggesting that the mechanism of the antiviral effect of HTyr might require the presence of a viral envelope [92].…”

Versatile iron–catechol-based nanoscale coordination polymers with antiretroviral ligand functionalization and their use as efficient carriers in HIV/AIDS therapy

“…MT-2 cells is an established cell line of CD4+ T cells, easier to manipulate and obtain than primary human cells, thus suitable for first line studies of anti-HIV effect and, therefore broadly used to test the efficacy experimental antiviral agents thanks to its high reproducibility. [50][51][52] HIV-1 exerts a profound cytopathic (CPE) effect against CD4+ T lymphocytes. Once infected, the lymphocytes accumulate viral DNA and actively produce HIV proteins, which results in the concomitant lysis of such infected cells by apoptosis.…”

Antiviral Functional Foods and Exercise Lifestyle Prevention of Coronavirus

“…Hydroxytyrosol antiviral mechanisms were showed through its inactivation effects on influenza A viruses, especially during the virus morphological changes, such as the presence of a viral envelope which is an integral membrane protein involved in several aspects of the virus life cycle including its assembly, budding, and pathogenesis [72]. The mechanisms of which OO nutraceuticals protect against viral infections have often focused on the hydroxytyrosol preventative effects on HIV from entering the host cell and binding the catalytic site of the HIV-1, and its inhibitory effect on both viral entry and integration [73]. Regular intake of olive leaf extracts, rich in polyphenol flavonoids, have been shown to be responsible for a 33% reduction in URI [74].…”