Abstract: The present invention relates to a new class of virus fusion inhibitors or virus entry inhibitors. More specifically the present invention relates to bivalent molecules that are pre-fusion inhibitors of viruses that makes use of the type (1) fusion mechanism belonging to the groups consisting of Othomyxoviridae, Paramyxoviridae, Retroviridae, Filoviridae and Coronaviridae, in particular HIV. The bivalent molecules of the present invention are molecules that comprise a first part capable of mimicking the function of a mammalian cell receptor, and a second part capable of binding to a virus, preferably HIV, resulting in the neutralization of the virus which is thus rendered harmless. Further, the present invention relates to compositions comprising the pre-fusion inhibitors, as well as to methods for obtaining the pre-fusion inhibitors and the use of the pre-fusion inhibitors.

Abstract: Immunogenic HIV-1 envelope polypeptides are provided, wherein specific amino acid residues are mutated to repress immunosuppression in GP41, thereby boosting the immune response against HIV-1. Specifically, mutation of those specific residues does not affect the fusogenic properties of the viral particle and/or the overall protein structure of the viral envelope protein. The invention further provides peptides and antigens based on the immunogenic HIV-1 envelopes as well as nucleic acid sequences and vectors encoding those. Moreover, biological entities such as viral particles are provided, as well as use of the provided components for preparation of a vaccine against HIV-1/AIDS.