Nanotechnology against human cytomegalovirus in vitro: polyanionic carbosilane dendrimers as antiviral agents

Abstract

Background Human cytomegalovirus (HCMV) is a worldwide infection, causing different troublesome in immunosupressed patients and very related to Human Immunodeficiency Virus 1 (HIV-1) infection, mainly in developing countries, with a co-infection rate of 80% in Africa. The high cost of present treatments and the lack of routinely tests in these countries urge the necessity to develop new molecules or strategies against HCMV. The new treatments should be low-cost and capable of avoiding the emerging problem of resistant virus. Nanoparticles play an important role in several viral infections. Our main focus is to study the potential activity of polyanionic carbosilane dendrimers (PDC), which are hyperbranched molecules with several sulfonate or sulfate groups in their periphery, against different viruses. Results We studied the activity of G1-S4, G2-S16 and G2-S24P PDCs in MRC-5 cell line against HCMV infection by several plaque reduction assays. Our results show that dendrimers present good biocompatibility at the concentrations tested (1–50 µM) for 6 days in cell culture. Interestingly, both G2-S16 and G2-S24P showed a remarked inhibition at 10 µM against HCMV infection. Results on attachment and virucidal assays indicated that the inhibition was not directed to the virus or the virus-cell attachment. However, results of time of addition, showed a longer lasting activity of these dendrimers in comparison to ganciclovir, and the combination of G2-S16 or G2-S24P with ganciclovir increases the HCMV inhibition around 90 %. Conclusions Nanotechnology, in particular polyanionic carbosilane dendrimers, have proved their potential application against HCMV, being capable of inhibiting the infection by themselves or enhancing the activity of ganciclovir, the actual treatment. These compounds represent a low-cost approach to fight HCMV infections.

Prevention of Herpesviridae Infections by Cationic PEGylated Carbosilane Dendrimers

“…Viral strain HSV-2 333 (GenBank accession number LS480640, NIH, Bethesda, MD, USA) and HCMV AD-169 (ATCC VR-538 TM , ATCC, Manassas, VA, USA) were grown and propagated in Vero and MRC-5 cells, respectively, and titrated by plaque assay with serial dilutions as previously described [ 28 , 29 ]. After ultracentrifugation, stock aliquots were stored at −80 °C.…”

Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection

“…All dendrimers ranged between 1 and 20 nm, becoming larger as the generation of the dendrimers increased. PCDs were synthesized and analyzed according to methods reported by the Dendrimers for Biomedical Applications Group of University of Alcalá (Madrid, Spain) NMR spectroscopy data confirming the identity of the compounds, and their structure and synthesis are presented in our previous articles [16]. Stock solutions of dendrimers (2.5 and 5 mM) and subsequent dilutions to working concentrations were prepared in nuclease-free water (Promega, Madrid, Spain).…”

“…In addition, dendrimer-based molecules have been recognized as an effective immunotherapy for viral infections, cancer, and autoimmune diseases due to their ability to efficiently capture and load antigens, their biocompatibility, and their versatility in various therapeutic applications [12]. Specifically, polyanionic carbosilane dendrimers (PCDs) have shown their ability to prevent the transmission of several sexually infectious diseases, such as Human Immunodeficiency Virus (HIV-1), Human Herpes Virus type 1 or 2 (HSV-1/HSV-2) or Hepatitis C Virus (HCV) [13][14][15], and even HCMV, as we have previously demonstrated [16]. Additionally, some PCDs have been shown to exert action on several cells of the immune system, such as anti-inflammatory treatments [17] or by increasing regulatory T cells' (Treg) capacity during HIV-1 infection [18].…”

Carbosilane dendritic nanostructures, highly versatile platforms for pharmaceutical applications

“…Anionic CBS dendrimers as G2‐S16 (Figure S10) are also efficient agents to prevent hepatitis C virus infection (Sepulveda‐Crespo et al, 2017), vaginal and human cytomegalovirus (Relano‐Rodríez et al, 2021), and herpes virus (Figure 3). These viruses are related to HIV, finding important coinfections rate with HIV in several countries.…”