Medical College of Shaoguan University, Shaoguan, 512026, Guangdong Province, China.
Key Laboratory of Industrial Microbiology, Ministry of Education, 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. 2020 Sep;495:108088. doi: 10.1016/j.carres.2020.108088. Epub 2020 Jun 26.
We report the preparation of multivalent amide-sialoside-decorated human serum albumin (HSA) and bovine serum albumin (BSA) as mimics of natural mucin and bioshields against influenza virus infection. Free sialic acid with an amine on C-2 was covalently attached to the protein scaffolds using di-(N-succinimidyl) adipate. Dynamic light scattering (DLS) showed that the synthetic neomucins were able to act as bioshields and aggregate the influenza virion particles. The dissociation constants (K) of the interactions between the prepared glycoconjugates and three different viral strains were measured by isothermal titration calorimetry (ITC) indicating the multivalent presentation of sialyl ligands on the HSA and BSA backbones can dramatically enhance the adsorbent capability compared to the corresponding monomeric sialoside. Hemagglutinin inhibition (HAI) and neuraminidase inhibition (NAI) assays showed that the glycoconjugates acted as moderate HA and NA inhibitors, thus impeding viral infection. Moreover, the different binding affinities of the glycoproteins to HA and NA proteins from different influenza viruses demonstrated the importance of HA/NA balance in viral replication and evolution. These findings provide a foundation for the development of antiviral drugs and viral adsorbent materials based on mimicking the structure of mucin.
我们报告了多价酰胺唾液酸修饰的人血清白蛋白（HSA）和牛血清白蛋白（BSA）的制备，作为天然粘蛋白的模拟物和抗流感病毒感染的生物盾牌。通过二（N-琥珀酰亚胺基）己二酸将带有 C-2 上氨基的游离唾液酸共价连接到蛋白质支架上。动态光散射（DLS）表明，合成的新粘蛋白能够作为生物盾牌并聚集流感病毒粒子。通过等温滴定微量热法（ITC）测量了制备的糖缀合物与三种不同病毒株之间相互作用的离解常数（K），表明唾液酸配体在 HSA 和 BSA 骨架上的多价呈现可以显著增强吸附剂的能力与相应的单价唾液酸相比。血凝素抑制（HAI）和神经氨酸酶抑制（NAI）测定表明，糖缀合物可作为中等 HA 和 NA 抑制剂，从而阻碍病毒感染。此外，糖蛋白与来自不同流感病毒的 HA 和 NA 蛋白的不同结合亲和力表明 HA/NA 平衡在病毒复制和进化中的重要性。这些发现为基于模拟粘蛋白结构开发抗病毒药物和病毒吸附材料提供了基础。
