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

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Glycopolymer with Sulfated Fucose and 6′-Sialyllactose as a Dual-Targeted Inhibitor on Resistant Influenza A Virus Strains
ACS Macro Letters ( IF 5.1 ) Pub Date : 2024-07-01 , DOI: 10.1021/acsmacrolett.4c00221
Ping Zhang _{1,

2} , Chenning Li ₃ , Xiaoyao Ma _{1,

2} , Jinfeng Ye _{1,

2} , Depeng Wang _{1,

2} , Hongzhi Cao _{1,

2,

4} , Guangli Yu _{1,

2,

4} , Wei Wang _{1,

2,

4} , Xun Lv ₃ , Chao Cai _{1,

2,

4}

Affiliation

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.

中文翻译：

含硫酸岩藻糖和 6′-唾液酸乳糖的糖聚合物作为抗甲型流感病毒株的双靶点抑制剂

甲型流感病毒（IAV）的频繁突变导致迫切需要开发创新的抗病毒药物。由于其生物相容性和结构多样性，糖聚合物在生物医学应用中具有显着的优势。然而，主要的挑战在于设计和合成明确的糖聚合物以精确控制其生物功能。在本研究中，通过开环复分解聚合和后修饰策略成功合成了含有硫酸化岩藻糖和6'-唾液酸乳糖的功能性糖聚合物。 MU-NANA 测定和血凝抑制数据证明，优化的杂聚物同时靶向 IAV 表面的血凝素和神经氨酸酶。抗病毒实验表明，该糖聚合物在体外对 H1N1 和 H3N2 亚型的野生型和突变株表现出广泛而有效的抑制活性，从而确立了其作为对抗 IAV 耐药性的双靶点抑制剂的潜力。

更新日期：2024-07-01

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