In the present study, we show that different cell types can respond to PSG1, secreting growth factors known to regulate vascular development and trophoblast behavior. In addition, the in vitro studies described here indicate that the interaction of PSG1 with endothelial cells can have functional consequences. Therefore, we propose that besides their ability to regulate the immune response, PSGs may have the previously unrecognized ability to contribute to the establishment of the vasculature during pregnancy. The precise processes during angiogenesis in the maternal-fetal unit that could be modulated by this family of proteins require further investigation. Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry. We report an approach for the computational design of peptide inhibitors of the dengue 2 virus (DENV-2) envelope (E) protein using high-resolution structural data from a pre-entry dimeric form of the protein. By using predictive strategies together with computational optimization of binding “pseudoenergies”, we were able to design multiple peptide sequences that showed low micromolar viral entry inhibitory activity. The two most active peptides, DN57opt and 1OAN1, were designed to displace regions in the domain II hinge, and the first domain I/domain II beta sheet connection, respectively, and show fifty percent inhibitory concentrations of 8 and 7 µM respectively in a focus forming unit assay. The antiviral peptides were shown to interfere with virus:cell binding, interact directly with the E proteins and also cause changes to the viral surface using biolayer interferometry and cryo-electron microscopy, respectively. These peptides may be useful for characterization of intermediate states in the membrane fusion process, investigation of DENV receptor molecules, and as lead compounds for drug discovery. Fusogenic viral envelope glycoproteins are multimeric proteins that facilitate the fusion of viral and target cell lipid membranes during the initiation of infection. The membrane fusion process is energetically favorable and essentially irreversible, but has a considerable kinetic energy barrier [1] . These proteins allow rapid membrane fusion by drawing the opposing membranes together and either stabilizing or providing the activation energy to surmount the transition state [1, 2] . In this way, they behave in many aspects like a fusion catalyst. Because they effect a macromolecular process that involves large scale conformational changes in the substrate membranes and the proteins themselves, these proteins possess multiple interacting surfaces that could be targeted by inhibitors [3] .