4.7 Article

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

Journal

JOURNAL OF NANOBIOTECHNOLOGY
Volume 19, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12951-021-00809-4

Keywords

Polyanionic carbosilane dendrimers; HCMV; Ganciclovir

Funding

  1. Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica [RD16/0025/0019, RD16CIII/0002/0002]
  2. Instituto de Salud Carlos III (ISCIII-Subdireccion General de Evaluacion)
  3. Fondo Europeo de Desarrollo Regional (FEDER) [RETIC PT17/0015/0042]
  4. Fondo de Investigacion Sanitaria (FIS)
  5. Comunidad de Madrid [PI16/01863, PI17/01115, PI17CIII/00003]
  6. Programa de Investigacion de la Consejeria de Sanidad de la Comunidad de Madrid - VI National RDi Plan
  7. Iniciativa Ingenio
  8. ISCIII
  9. European Regional Development Fund
  10. EUROPARTNER: Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection for interdisciplinary research and innovation of the University of Lodz Programme: NAWA International Academic Partnership
  11. COST Action [CA 17140]
  12. COST (European Cooperation in Science and Technology)
  13. Instituto de Salud Carlos III [CP14/0010, CP17CIII/00007]
  14. Instituto de Salud Carlos III, Spanish Healt Ministry
  15. Plan Nacional R+D+I
  16. ISCIII- Subdireccion General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER) - Instituto de Salud Carlos III through the Red Tematica de Investigacion Cooperativa en SIDA [RIS C03/173, RD12/0017/0018, RD16/0002/0006]
  17. ISCIII-Subdireccion General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER)

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Polyanionic carbosilane dendrimers have shown potential application in inhibiting HCMV infection and enhancing the activity of current treatments, representing a low-cost approach to fight HCMV infections.
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 mu M) for 6 days in cell culture. Interestingly, both G2-S16 and G2-S24P showed a remarked inhibition at 10 mu M 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.

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