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抗SARS-CoV-2的稳定的、马来酰亚胺功能化肽脂质体的研发

Development of Stable, Maleimide-Functionalized Peptidoliposomes Against SARS-CoV-2.

作者信息

Michel Olga, Kaczorowska Aleksandra, Matusewicz Lucyna, Piórkowska Kliwia, Golec Marlena, Fus Wiktoria, Kuliczkowski Kazimierz, Sikorski Aleksander F, Czogalla Aleksander

机构信息

Department of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, F. Joliot Curie 14a, 50-383 Wrocław, Poland.

Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wrocław University of Science and Technology, Wybrzeże S. Wyspiańskiego 27, 50-370 Wrocław, Poland.

出版信息

Int J Mol Sci. 2025 Feb 14;26(4):1629. doi: 10.3390/ijms26041629.

Abstract

Throughout the last 5 years, extensive research has been carried out towards the development of effective treatments for coronavirus disease 2019 (COVID-19). Regardless of the worldwide efforts, only a few drugs have passed clinical trials, and there is still a need to develop therapies, especially for those who are particularly vulnerable to a severe disease course. Maleimide-functionalized liposomes are proposed to serve as a platform for the immobilization, stabilization, and delivery of a short peptide sequence with high affinity towards severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, extensive optimizations should be performed in order to achieve features required for a reliable drug candidate, such as homogeneity of physical parameters and their long-term stability. Here, we present a step-by-step development process for maleimide-functionalized liposomes, which-once decorated with the SARS-CoV-2-binding peptide-could inhibit the infection progress of COVID-19. The main emphasis is placed on defining optimal lipid composition and formation conditions of PEGylated liposomes. We propose that the developed nanocarrier technology can be used as a universal platform for the construction of multiple antiviral agents.

摘要

在过去的5年里,针对2019冠状病毒病(COVID-19)有效治疗方法的开发进行了广泛研究。尽管全球都在努力,但只有少数药物通过了临床试验,仍然需要开发治疗方法,特别是针对那些特别容易出现严重病程的患者。有人提出,马来酰亚胺功能化脂质体可作为一个平台,用于固定、稳定和递送对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)具有高亲和力的短肽序列。然而,为了实现可靠候选药物所需的特性,如物理参数的均匀性及其长期稳定性,需要进行广泛的优化。在此,我们展示了马来酰亚胺功能化脂质体的逐步开发过程,该脂质体一旦用SARS-CoV-2结合肽修饰,就可以抑制COVID-19的感染进程。主要重点是确定聚乙二醇化脂质体的最佳脂质组成和形成条件。我们认为,所开发的纳米载体技术可作为构建多种抗病毒药物的通用平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b8a/11855074/08743a415baf/ijms-26-01629-g001.jpg

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