关键词: Antiviral Dendrimers Inhibitors Peptides SARS-CoV-2

来  源:   DOI:10.1016/j.ijpharm.2024.124389

Abstract:
We have recently witnessed that considerable progresses have been made in the rapid detection and appropriate treatments of COVID-19, but still this virus remains one of the main targets of world research. Based on the knowledge of the complex mechanism of viral infection we designed peptide-dendrimer inhibitors of SARS-CoV-2with the aim to block cell infection through interfering with the host-pathogen interactions. We used two different strategies: i) the first one aims at hindering the virus anchorage to the human cell; ii) the second -strategy points to interfere with the mechanism of virus-cell membrane fusion. We propose the use of different nanosized carriers, formed by several carbosilane dendritic wedges to deliver two different peptides designed to inhibit host interaction or virus entry. The antiviral activity of the peptide-dendrimers, as well as of free peptides and free dendrimers was evaluated through the use of SARS-CoV-2 pseudotyped lentivirus. The results obtained show that peptides designed to block host-pathogen interaction represent a valuable strategy for viral inhibition.
摘要:
我们最近目睹了在COVID-19的快速检测和适当治疗方面取得了相当大的进展,但这种病毒仍然是世界研究的主要目标之一。基于对病毒感染复杂机制的了解,我们设计了SARS-CoV-2的肽-树枝状聚合物抑制剂,旨在通过干扰宿主-病原体相互作用来阻断细胞感染。我们使用了两种不同的策略:i)第一种旨在阻碍病毒锚定到人类细胞;ii)第二种策略指向干扰病毒-细胞膜融合的机制。我们建议使用不同的纳米载体,由几个碳硅烷树状楔形物形成,以递送两种不同的肽,旨在抑制宿主相互作用或病毒进入。肽-树枝状聚合物的抗病毒活性,通过使用SARS-CoV-2假型化慢病毒评估游离肽和游离树状聚合物。获得的结果表明,设计用于阻断宿主-病原体相互作用的肽代表了一种有价值的病毒抑制策略。
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