Section Head Immunology, Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón (HGUGM), Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
J Nanobiotechnology. 2021 Mar 3;19(1):65. doi: 10.1186/s12951-021-00809-4.
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.
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 %.
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.
人类巨细胞病毒（HCMV）是一种全球性感染，在免疫抑制患者中引起不同的麻烦，与人类免疫缺陷病毒 1（HIV-1）感染密切相关，主要在发展中国家，在非洲的合并感染率为 80%。目前治疗的高成本和这些国家缺乏常规检测促使人们有必要开发针对 HCMV 的新分子或策略。新的治疗方法应该成本低廉，并能够避免出现耐药病毒的新问题。纳米颗粒在几种病毒感染中起着重要作用。我们的主要重点是研究聚阴离子碳硅烷树枝状大分子（PDC）的潜在活性，这些树枝状大分子在其外围具有几个磺酸根或硫酸根，针对不同的病毒。
我们通过几种噬斑减少测定法研究了 MRC-5 细胞系中 G1-S4、G2-S16 和 G2-S24P PDC 对 HCMV 感染的活性。我们的结果表明，树枝状大分子在细胞培养中测试的浓度（1-50 μM）下具有良好的生物相容性，持续 6 天。有趣的是，G2-S16 和 G2-S24P 在 10 μM 时对 HCMV 感染均表现出明显的抑制作用。附着和病毒杀伤测定的结果表明，抑制不是针对病毒或病毒-细胞附着。然而，添加时间的结果表明，与更昔洛韦相比，这些树枝状大分子具有更长的持续活性，并且 G2-S16 或 G2-S24P 与更昔洛韦的组合可将 HCMV 抑制提高约 90%。
纳米技术，特别是聚阴离子碳硅烷树枝状大分子，已证明其在抑制 HCMV 方面具有潜在的应用，它们本身能够抑制感染，或增强更昔洛韦的活性，即目前的治疗方法。这些化合物代表了一种对抗 HCMV 感染的低成本方法。
