Glycopolymer with Sulfated Fucose and 6′-Sialyllactose as a Dual-Targeted Inhibitor on Resistant Influenza A Virus Strains

IF 5.1 Q1 POLYMER SCIENCE

ACS Macro Letters Pub Date : 2024-07-01 DOI:10.1021/acsmacrolett.4c00221

Ping Zhang, Chenning Li, Xiaoyao Ma, Jinfeng Ye, Depeng Wang, Hongzhi Cao, Guangli Yu, Wei Wang*, Xun Lv* and Chao Cai*,

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Abstract

The frequent mutations of influenza A virus (IAV) have led to an urgent need for the development of innovative antiviral drugs. Glycopolymers offer significant advantages in biomedical applications owing to their biocompatibility and structural diversity. However, the primary challenge lies in the design and synthesis of well-defined glycopolymers to precisely control their biological functionalities. In this study, functional glycopolymers with sulfated fucose and 6′-sialyllactose were successfully synthesized through ring-opening metathesis polymerization and a postmodification strategy. The optimized heteropolymer exhibited simultaneous targeting of hemagglutinin and neuraminidase on the surface of IAV, as evidenced by MU-NANA assay and hemagglutination inhibition data. Antiviral experiments demonstrated that the glycopolymer displayed broad and efficient inhibitory activity against wild-type and mutant strains of H1N1 and H3N2 subtypes in vitro, thereby establishing its potential as a dual-targeted inhibitor for combating IAV resistance.

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含硫酸化岩藻糖和 6'-Sialyllactose 的聚糖作为抗性甲型流感病毒株的双靶向抑制剂。

甲型流感病毒（IAV）的频繁变异导致人们迫切需要开发创新型抗病毒药物。由于具有生物兼容性和结构多样性，糖聚合物在生物医学应用方面具有显著优势。然而，如何设计和合成定义明确的糖聚合物，以精确控制其生物功能，是目前面临的主要挑战。本研究通过开环元合成聚合和后修饰策略，成功合成了硫酸化岩藻糖和 6'-sialyllactose 的功能性糖聚合物。从 MU-NANA 分析和血凝抑制数据可以看出，优化后的杂多聚合物能同时靶向 IAV 表面的血凝素和神经氨酸酶。抗病毒实验表明，该聚糖在体外对 H1N1 和 H3N2 亚型的野生型和突变株具有广泛而有效的抑制活性，从而确立了其作为双靶向抑制剂对抗 IAV 抗药性的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Macro Letters 化学-

CiteScore

10.40

自引率

3.40%

发文量

209

审稿时长

1 months

期刊介绍： ACS Macro Letters publishes research in all areas of contemporary soft matter science in which macromolecules play a key role, including nanotechnology, self-assembly, supramolecular chemistry, biomaterials, energy generation and storage, and renewable/sustainable materials. Submissions to ACS Macro Letters should justify clearly the rapid disclosure of the key elements of the study. The scope of the journal includes high-impact research of broad interest in all areas of polymer science and engineering, including cross-disciplinary research that interfaces with polymer science. With the launch of ACS Macro Letters, all Communications that were formerly published in Macromolecules and Biomacromolecules will be published as Letters in ACS Macro Letters.