The aim of this work was to evaluate the mechanism of action of diterpenes isolated from brown algaes of the Brazilian shore on the “in vitro” replication of Herpes Simples type-1 (HSV-1). We have evaluated the effect of secondary metabolites from Dictyota menstrualis (DA-1), Dictyota pfaffii (Dolabellano-2) and Stypopodium zonale (SP) on HSV-infected Vero cells. These cells were infected for 1h at 37^oC and 5% CO₂ and treated with the derivatives at 50μM (DA-1 and Dolabellano- 2), or at 2μg/mL (SP). They inhibited HSV-1 cytophatic effect about 90% at these concentrations. In order to perform the citotoxicity assay (CC₅₀), Vero cells were treated with increasing concentrations of the compounds during 72h. This assay was performed by Trypan blue and MTT approaches, resulting in values about 200μM for Dolabellano-2, 1000μM for DA-1 and more than 200μg/mL for SP. In order to determine the EC₅₀, viruses were yielded at MOI of 1 with various concentrations of the compounds, showing an EC₅₀ of 0.7μM for DA-1 and about 1.0μM for Dolabellano-2. The time-course assay indicates that the best inhibitory condition was achieved at 3-6 h post-infection, suggesting that both molecules are early phase inhibitors. At this assay Vero cells were infected with HSV-1 and treated with 1 μM of the compounds at different steps of viral replication (adsorption, penetration, 0-3hp.i., 3-6hp.i. and 6-20hp.i.). The protein synthesis of infected Vero cells was analyzed using [³⁵S]-methionine and we observed that DA-1 and Dolabellano-2 prevented host-cell protein shut-off induced by HSV-1; this effect seems to be MOI dependent for DA-1. We could observe that DA-1 was more selective as an anti-herpetic compound than Dolabellano-2, since the former compound has shown lower cytotoxicity than the latter. Further experiments are now in progress to evaluate the real target o fthese compounds on early phase of HSV-1 replication.