Cationic Dendrimer G2-S16 Inhibits Herpes Simplex Type 2 Infection and Protects Mice Vaginal Microbiome

Abstract

The G2-S16 polyanionic carbosilane dendrimer is a promising microbicide that inhibits HSV-2 infection in vitro and in vivo in mice models. This G2-S16 dendrimer inhibits HSV-2 infection even in the presence of semen. Murine models, such as BALB/c female mice, are generally used to characterize host-pathogen interactions within the vaginal tract. However, the composition of endogenous vaginal flora remains largely undefined with modern microbiome analyses. It is important to note that the G2-S16 dendrimer does not change healthy mouse vaginal microbiome where Pseudomonas (10.2–79.1%) and Janthinobacterium (0.7–13%) are the more abundant genera. The HSV-2 vaginally infected female mice showed a significant microbiome alteration because an increase of Staphylococcus (up to 98.8%) and Escherichia (30.76%) levels were observed becoming these bacteria the predominant genera. BALB/c female mice vaginally-treated with the G2-S16 dendrimer and infected with the HSV-2 maintained a healthy vaginal microbiome similar to uninfected female mice. Summarizing, the G2-S16 polyanionic carbosilane dendrimer inhibits the HSV-2 infection in the presence of semen and prevents the alteration of mice female vaginal microbiome.

Role of G2-S16 Polyanionic Carbosilane Dendrimer in the Prevention of Respiratory Syncytial Virus Infection In Vitro and In Vivo in Mice

“…All these data demonstrate that the G2-S16 dendrimer is capable of interacting with host cellular receptors implied in the RSV infection. We previously described that G2-S16 dendrimer interacts with cellular HS and HBD in HSV infection [ 34 , 35 , 36 , 37 ]. We also previously described that the G2-S16 dendrimer could interact electrostatically with the viral glycoproteins of the viral surface as well as cellular receptors [ 21 , 22 ].…”

G2-S16 Polyanionic Carbosilane Dendrimer Can Reduce HIV-1 Reservoir Formation by Inhibiting Macrophage Cell to Cell Transmission

“…In conclusion, our results indicates that G2-S16 dendrimer can act in different stages of HIV-1 infection. The main objective of G2-S16 dendrimer is its use as a microbicide, creating a physical barrier that protects the vaginal mucosa from being disrupted [33,34] and inhibiting several viral infections [35][36][37][38]. Thus, these results exacerbate the applicability of this G2-S16 dendrimer, as it is capable of inhibiting macrophages from spreading to other target cells, minimizing viral charge [39], as well as reducing viral reservoirs and sanctuaries due to the ability of macrophages to deliver viral particles to different anatomic targets.…”

Nanotechnological strategies for systemic microbial infections treatment: A review

“…Date from work developed by Guerrero-Beltrán et al (2020) indicated that G2-S16 polyanionic carbosilane dendrimer presents relevant in vitro and in vivo inhibitory activity against herpes simplex type 2 (HSV-2) infection, with complete inhibition of HSV-2 (>90%). Moreover, the G2-S16 provided protection to mice vaginal microbiome, once the composition of vaginal microbiome was similar to healthy mice.…”