Carbosilane dendrons with fatty acids at the core as a new potential microbicide against HSV-2/HIV-1 co-infection

Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) represent the two most frequent sexually transmitted infections (STI) worldwide. Epidemiological studies suggest that HSV-2 increases the risk of HIV-1 acquisition approximately 3-fold mainly due to the clinical and...

Full description

Saved in:
Bibliographic Details
Published in:Nanoscale 2017-11, Vol.9 (44), p.17263-17273
Main Authors: Guerrero-Beltrán, C, Ceña-Diez, R, Sepúlveda-Crespo, D, De la Mata, J, Gómez, R, Leal, M, Muñoz-Fernández, M. A, Jiménez, J. L
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents - pharmacology
Cercopithecus aethiops
Coinfection - drug therapy
Coinfection - virology
Dendrimers - chemistry
Epidemiology
Fatty acids
Fatty Acids - chemistry
Herpes Genitalis - drug therapy
Herpesvirus 2, Human - drug effects
HIV
HIV Infections - drug therapy
HIV-1 - drug effects
Human immunodeficiency virus
Humans
Immunology
Infections
Plants, Medicinal
Silanes - pharmacology
Vaccines
Vero Cells
Viability
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) represent the two most frequent sexually transmitted infections (STI) worldwide. Epidemiological studies suggest that HSV-2 increases the risk of HIV-1 acquisition approximately 3-fold mainly due to the clinical and immunological manifestations. In the absence of vaccines against both STI, the development of new preventive strategies has become essential for further studies. We performed the screening of six novel polyanionic carbosilane dendrons to elucidate their potential activity against HSV-2/HIV-1 co-infection and their mechanism of action. These new nanoparticles are carbosilane branched dendrons from first to third generation, with palmitic or hexanoic fatty acids as the core and capped with sulfonate groups, named G1 d -STE2Hx, G2 d -STE4Hx, G3 d -STE8Hx, G1 d -STE2Pm, G2 d -STE4Pm and G3 d -STE8Pm. G3 d -STE8Hx and G3 d -STE8Pm carbosilane branched dendrons showed high viability. These dendrons also showed a great broad-spectrum antiviral activity, as well as a suitable efficacy against HIV-1 even if the mucosal disruption occurs as a consequence of HSV-2 infection. Our results exert high inhibition against HSV-2 and HIV-1 by blocking the entry of both viruses with the median effective concentration EC 50 values in the nanomolar range. Additionally, G3 d -STE8Hx and G3 d -STE8Pm retained their anti-HSV-2/HIV-1 activity at different pH values. G3 d -STE8Hx and G3 d -STE8Pm dendrons may be potential candidates as dual-acting microbicides against HSV-2/HIV-1 co-infection. The development of a HSV-2/HIV-1 co-infection in vitro model (a): dendrons prevented HIV-1 infection even if mucosal disruptions occur as a consequence of HSV-2 infection (b).
ISSN:2040-3364
2040-3372
DOI:10.1039/c7nr05859d