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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Thiosialoside-decorated polymers use a two-step mechanism to inhibit both early and late stages of influenza virus infection
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Thiosialoside-decorated polymers use a two-step mechanism to inhibit both early and late stages of influenza virus infection

机译：装饰性聚合物使用两步机制来抑制流感病毒感染的早期和晚期阶段

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摘要

We describe the preparation of thiosialoside-modified poly (methyl vinyl ether-alt-maleic anhydride) as second-generation polymeric conjugates for the inhibition of influenza virus infection. These synthetic glycopolymers show significantly enhanced neuraminidase inhibitory and antiviral activity in enzyme and cellular levels, respectively. The polyvalent thiosialosides also exhibit comparable inhibitory activity to the first-line anti-influenza drugs Zanamivir (R) and Oseltamivir (R) against the PR8 influenza virus strain in virus growth inhibition assays, which may be attributed to multivalent binding to neuraminidase on the virion particles, leading to the virion aggregation and further inhibiting the attaching/fusion and releasing steps in the influenza virus life-cycle. These findings suggest that attaching monomeric sialoside with neuraminidase inhibitory activity to a polymeric scaffold will synergistically disturb both the early and late stages of influenza virus infection, and provides a basis for the development of efficacious anti-viral agents against both wild-type and drug-resistant mutant strains. (C) 2020 Elsevier Masson SAS. All rights reserved.
机译：我们描述了用于抑制流感病毒感染的第二代聚合物缀合物的硫代肌苷改性聚（甲基乙烯基醚 - ALT-马来酸酐）的制备。这些合成甘醇聚合物分别显示出显着增强的酶和细胞水平的神经氨酸酶抑制和抗病毒活性。多价噻吩醇素还针对病毒生长抑制测定中的PR8流感病毒菌株对第一线抗流感药物Zanamivir（R）和Oseltamivir（R）表现出可比较的抑制活性，这可能归因于在病毒赛中对神经氨酸酶的多价结合颗粒，导致病毒虫聚集并进一步抑制流感病毒生命周期中的附着/融合和释放步骤。这些发现表明，用神经氨酸酶抑制活性与聚合物支架将单体唾液酸盐溶解将协同干扰流感病毒感染的早期和晚期阶段，并为野生型和药物的有效抗病毒剂的发展提供了基础抗性突变菌株。 （c）2020 Elsevier Masson SAS。版权所有。

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