Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1 Entry and Cell to Cell Fusion
Autor: | Francisco Javier de la Mata, Ma Jesús Serramía, Ingrid Araya-Durán, Rafael Gómez, Valeria Márquez-Miranda, Fernando D. González-Nilo, M. Ángeles Muñoz-Fernández, Carlos Guerrero-Beltrán, Ignacio Rodriguez-Izquierdo, Manuel Leal |
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Rok vydání: | 2018 |
Předmět: |
Anions
Models Molecular 0301 basic medicine Dendrimers Anti-HIV Agents viruses Cell Biomedical Engineering Pharmaceutical Science HIV Infections Bioengineering Context (language use) 02 engineering and technology HIV Envelope Protein gp120 Cell Line 03 medical and health sciences Multinucleate Dendrimer medicine Humans Pharmacology Syncytium Cell fusion Chemistry Organic Chemistry virus diseases Silanes Virus Internalization 021001 nanoscience & nanotechnology Fusion protein Cell biology 030104 developmental biology medicine.anatomical_structure Cell culture CD4 Antigens HIV-1 0210 nano-technology Biotechnology |
Zdroj: | Bioconjugate Chemistry. 29:1584-1594 |
ISSN: | 1520-4812 1043-1802 |
Popis: | Cell-to-cell transmission is the most effective pathway for the spread of human immunodeficiency virus (HIV-1). Infected cells expose virus-encoded fusion proteins on their surface as a consequence of HIV-1 replicative cycle that interacts with noninfected cells through CD4 receptor and CXCR4 coreceptor leading to the formation of giant multinucleated cells known as syncytia. Our group previously described the potent activity of dendrimers against CCR5-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 significantly reduced 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. |
Databáze: | OpenAIRE |
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