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The antiviral effect of the CH2Cl2/MeOH-soluble fraction from the alga Dictyota menstrualis on HIV-1 replication was evaluated in vitro. The antiretroviral activity was attributed to two diterpenes: (6R)-6-hydroxydichotoma-3,14-diene-1,17-dial, named Da-1, and (6R)-6-acetoxi-dichotoma-3,14-diene-1,17-dial, named AcDa-1. Da-1 or AcDa-1 were added to the culture medium of HIV-1-infected PM-1 cells at different times post-infection or during virus adsorption/penetration. The results indicated that the compounds affected an early step of the virus replicative cycle. Virus binding and entry into the host cells were evaluated in the presence of each diterpene, but no inhibitory effect was observed. To evaluate provirus DNA synthesis/integration into the host genome, the viral protease coding sequence was amplified from total cellular DNA. Proviral DNA was not detected in infected cells incubated with the diterpenes. To investigate the effect of the diterpenes on the reverse transcription of the viral genomic RNA, the recombinant HIV-1 reverse transcriptase (RT) was assayed in vitro in the presence of each diterpene. Da-1 and AcDa-1 inhibited the RNA-dependent DNA-polymerase activity of HIV-1 RT in a dose-dependent manner. Taken together, our results demonstrate that both diterpenes inhibit HIV-1 RT and consequently virus replication. [Copyright &y& Elsevier]