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. 2016 Nov 28;30(18):2767-2776.
doi: 10.1097/QAD.0000000000001283.

Hydroxytyrosol: A New Class of Microbicide Displaying Broad anti-HIV-1 Activity

Free PMC article

Hydroxytyrosol: A New Class of Microbicide Displaying Broad anti-HIV-1 Activity

Luis M Bedoya et al. AIDS. .
Free PMC article


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.


Fig. 1
Fig. 1
(a) Evaluation of the anti-HIV activity of 5-hydroxytyrosol in MT-2 cells, TZM-Luc cells and human primary peripheral blood mononuclear cells preactivated with PHA/interleukin-2.
Fig. 2
Fig. 2
Combination effect in anti-HIV activity of 5-hydroxytyrosol and tenofovir or emtricitabine or lamivudine in MT-2 cells and peripheral blood mononuclear cells preactivated with PHA/interleukin-2 infected with NL4.3-Ren.
Fig. 3
Fig. 3
Evaluation of the anti-HIV activity 5-hydroxytyrosol in resistant HIV to NRTIs (K65R, M184V and double resistant), multiresistant HIV (NRTIs, NNRTIs and protease inhibitors) and integrase inhibitors resistant (Q148K) in infections of MT-2 cells and reactivated peripheral blood mononuclear cells.
Fig. 4
Fig. 4
5-Hydroxytyrosol activity on A, C, D, E, F and G HIV-1 subtypes and founder viruses S5.1, S8.1 and S14 (6.1) on cell lines and preactivated peripheral blood mononuclear cells.

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