Research Centre of Modern Analytical Technology, Tianjin University of Science & Technology, No. 29, 13th Avenue, TEDA, Tianjin, 300457, China.
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, No. 29, 13th Avenue, TEDA, Tianjin, 300457, China.
Carbohydr Res. 2022 Oct;520:108631. doi: 10.1016/j.carres.2022.108631. Epub 2022 Jul 8.
The preparation of oseltamivir-bovine serum albumin conjugate (OS-BSA) for use as a multivalent influenza neuraminidase (NA) inhibitor is reported. Briefly, the oseltamivir azidohexyl ester was synthesized and covalently bound via an orthogonal attachment to bicyclononyne-modified BSA using copper-free click chemistry. Primary antiviral assays on NA protein and cellular levels showed that the synthetic multivalent OS-BSA conjugate was a more effective inhibitor than monomeric OS azidohexyl ester. Further investigation of the antiviral mechanism found that the prepared OS-BSA could not only be used as a multivalent NA inhibitor but also acted as an adsorbent for the aggregation of virion particles, contributing to the inhibition of the influenza viral replication cycle. Our findings provide insight into the antiviral mechanism of multivalent NA inhibitors and form a basis for the development of novel antiviral agents.
报道了一种用于作为多价流感神经氨酸酶（NA）抑制剂的奥司他韦-牛血清白蛋白缀合物（OS-BSA）的制备。简要地说，通过无铜点击化学将奥司他韦叠氮己基酯通过正交连接共价结合到双环壬炔修饰的 BSA 上合成。在 NA 蛋白和细胞水平上的初步抗病毒测定表明，合成的多价 OS-BSA 缀合物比单体 OS 叠氮己基酯更有效。对抗病毒机制的进一步研究发现，所制备的 OS-BSA 不仅可以用作多价 NA 抑制剂，而且还可以作为病毒粒子聚集的吸附剂，有助于抑制流感病毒复制周期。我们的研究结果深入了解了多价 NA 抑制剂的抗病毒机制，并为新型抗病毒药物的开发奠定了基础。
