2026-04-29T04:08:33Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/102472024-10-24T12:57:24Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Bedoya, Luis M author Beltran, Manuela author Obregon-Calderon, Patricia author García-Pérez, Javier author de la Torre-Tarazona, Humberto Erick author Gonzalez-Fernandez, Nuria author Perez-Olmeda, Mayte author Auñón, David author Capa, Laura author Gómez-Acebo, Eduardo author Alcamí, José author 2016 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. AIDS. 2016 Nov 28;30(18):2767-2776. 0269-9370 http://hdl.handle.net/20.500.12105/10247 27677167 10.1097/QAD.0000000000001283 1473-5571 AIDS (London, England) Hydroxytyrosol: a new class of microbicide displaying broad anti-HIV-1 activity