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聚(乙二醇)聚(4-苯乙烯磺酸钠)共聚物作为有效的寨卡病毒抑制剂:研究

Poly(ethylene glycol)poly(sodium 4-styrenesulfonate) Copolymers as Efficient Zika Virus Inhibitors: Studies.

作者信息

Botwina Paweł, Obłoza Magdalena, Bonarek Piotr, Szczubiałka Krzysztof, Pyrć Krzysztof, Nowakowska Maria

机构信息

Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland.

Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.

出版信息

ACS Omega. 2023 Feb 9;8(7):6875-6883. doi: 10.1021/acsomega.2c07610. eCollection 2023 Feb 21.

Abstract

A series of poly(ethylene glycol)--poly(sodium 4-styrenesulfonate) (PEG--PSSNa) copolymers were synthesized, and their antiviral activity against Zika virus (ZIKV) was determined. The polymers inhibit ZIKV replication in mammalian cells at nontoxic concentrations. The mechanistic analysis revealed that the PEG-PSSNa copolymers interact directly with viral particles in a zipper-like mechanism, hindering their interaction with the permissive cell. The antiviral activity of the copolymers is well-correlated with the length of the PSSNa block, indicating that the copolymers' ionic blocks are biologically active. The blocks of PEG present in copolymers studied do not hinder that interaction. Considering the practical application of PEG--PSSNa and the electrostatic nature of the inhibition, the interaction between the copolymers and human serum albumin (HSA) was evaluated. The formation of PEG--PSSNa-HSA complexes in the form of negatively charged nanoparticles well-dispersed in buffer solution was observed. That observation is promising, given the possible practical application of the copolymers.

摘要

合成了一系列聚(乙二醇)-聚(4-苯乙烯磺酸钠)(PEG-PSSNa)共聚物,并测定了它们对寨卡病毒(ZIKV)的抗病毒活性。这些聚合物在无毒浓度下可抑制哺乳动物细胞中的ZIKV复制。机理分析表明,PEG-PSSNa共聚物以拉链样机制直接与病毒颗粒相互作用,阻碍它们与易感细胞的相互作用。共聚物的抗病毒活性与PSSNa嵌段的长度密切相关,表明共聚物的离子嵌段具有生物活性。所研究的共聚物中存在的PEG嵌段不会阻碍这种相互作用。考虑到PEG-PSSNa的实际应用以及抑制作用的静电性质,评估了共聚物与人血清白蛋白(HSA)之间的相互作用。观察到以带负电荷的纳米颗粒形式形成的PEG-PSSNa-HSA复合物在缓冲溶液中分散良好。鉴于共聚物可能的实际应用,这一观察结果很有前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ff/9948194/78c4227b9f13/ao2c07610_0002.jpg

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