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ANIONIC CARBOSILANE DENDRIMERS DESTABILIZE THE GP120-CD4 COMPLEX BLOCKING HIV-1 ENTRY AND CELL TO CELL FUSION.

ANIONIC CARBOSILANE DENDRIMERS DESTABILIZE THE GP120-CD4 COMPLEX BLOCKING HIV-1 ENTRY AND CELL TO CELL FUSION.
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Guerrero-Beltrán C, Rodríguez-Izquierdo I, Serramía MJ, Araya-Duran I, Márquez-Miranda V, Gómez R, de la Mata FJ, Leal M, Gonzalez-Nilo FD, Muñoz-Fernández MÁ,


Guerrero-Beltrán C, Rodríguez-Izquierdo I, Serramía MJ, Araya-Duran I, Márquez-Miranda V, Gómez R, de la Mata FJ, Leal M, Gonzalez-Nilo FD, Muñoz-Fernández MÁ, (click to view)

Guerrero-Beltrán C, Rodríguez-Izquierdo I, Serramía MJ, Araya-Duran I, Márquez-Miranda V, Gómez R, de la Mata FJ, Leal M, Gonzalez-Nilo FD, Muñoz-Fernández MÁ,

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Bioconjugate chemistry 2018 03 23() doi 10.1021/acs.bioconjchem.8b00106

Abstract

Cell-to-cell transmission is the most effective pathway for human immunodeficiency virus (HIV-1) spread. Infected cells expose virus-encoded fusion proteins on their surface as consequence of HIV-1 replicative cycle that interacts with non-infected cells through CD4 receptor and CXCR4 co-receptor leading to the formation of giant multinucleated cells known as syncytia. Our group previously described the potent activity of dendrimers against R5-tropic viruses. Nevertheless, the study of G1-S4, G2-S16 and G3-S16 dendrimers in the context of X4-HIV-1 tropic cell-cell fusion referred to syncytium formation remains still unknown. These dendrimers showed a suitable biocompatibility in all cell lines studied and our results demonstrated that anionic carbosilane dendrimers G1-S4, G2-S16 and G3-S16 significantly inhibit the X4-HIV-1 infection, as well as syncytia formation, in a dose dependent manner. We also demonstrated that G2-S16 and G1-S4 reduced significantly syncytia formation in HIV-1 Env-mediated cell-to-cell fusion model. Molecular modeling and in silico models showed that G2-S16 dendrimer interfered with gp120-CD4 complex and demonstrated its potential use for a treatment.

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