Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1.
Nanotechnology-derived platforms, such as dendrimers, are very attractive in several biological applications. In the case of human immunodeficiency virus (HIV) infection, polyanionic carbosilane dendrimers have shown great potential as antiviral agents in the development of novel microbicides to prevent the sexual transmission of HIV-1. In this work, we studied the mechanism of two sulfated and naphthylsulfonated functionalized carbosilane dendrimers, G3-S16 and G2-NF16. They are able to inhibit viral infection at fusion and thus at the entry step. Both compounds impede the binding of viral particles to target cell surface and membrane fusion through the blockage of gp120-CD4 interaction. In addition, and for the first time, we demonstrate that dendrimers can inhibit cell-to-cell HIV transmission and difficult infectious synapse formation. Thus, carbosilane dendrimers' mode of action is a multifactorial process targeting several proteins from viral envelope and from host cells that could block HIV infection at different stages during the first step of infection.
Molecular Immunobiology Laboratory, General Universitary Hospital Gregorio Marañon, Madrid, Spain; Health Research Institute Gregorio Marañon, Madrid, Spain; Spanish HIV HGM BioBanK, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
Enrique
E
Vacas-Córdoba
Faculty of Science, Jan Evangelista Purkyně University, Ústí nad Labem, Czech Republic; Laboratory of Applied Mathematics and Physics (LaMFI), University of Applied Sciences and Arts of Southern Switzerland, Manno, Switzerland.
Marek
M
Maly
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Dendrimers for Biomedical Applications Group (BioInDen), University of Alcalá, Alcalá de Henares, Madrid, Spain.
Francisco J
FJ
De la Mata
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Dendrimers for Biomedical Applications Group (BioInDen), University of Alcalá, Alcalá de Henares, Madrid, Spain.
Rafael
R
Gómez
Molecular Immunobiology Laboratory, General Universitary Hospital Gregorio Marañon, Madrid, Spain; Health Research Institute Gregorio Marañon, Madrid, Spain; Spanish HIV HGM BioBanK, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
Marjorie
M
Pion
Molecular Immunobiology Laboratory, General Universitary Hospital Gregorio Marañon, Madrid, Spain; Health Research Institute Gregorio Marañon, Madrid, Spain; Spanish HIV HGM BioBanK, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
M Ángeles
MÁ
Muñoz-Fernández
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D050091:Dendrimers / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D008958:Models, Molecular; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry*; D012821:Silanes / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D050091:Dendrimers; D015699:HIV Envelope Protein gp120; D000071228:Polyelectrolytes; D011108:Polymers; D012821:Silanes; C504072:carbosilane
HIV; carbosilane dendrimer; mechanism; microbicide; nanotechnology