Biomacromolecules 2011 Nov;12 (11): 3962-9. [IF:5.325]
Carbohydrate-functionalized chitosan fiber for influenza virus capture.
Li X , Wu P , Gao GF , Cheng S .
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China.
北京中国科学院微生物所病原微生物与免疫学重点实验室
Abstract
The high transmissibility and genetic variability of the influenza virus have made the design of effective approaches to control the infection particularly challenging. The virus surface hemagglutinin (HA) protein is responsible for the viral attachment to the host cell surface via the binding with its glycoligands, such as sialyllactose (SL), and thereby is an attractive target for antiviral designs. Herein we present the facile construction and development of two SL-incorporated chitosan-based materials, either as a water-soluble polymer or as a functional fiber, to demonstrate their abilities for viral adhesion inhibition and decontamination. The syntheses were accomplished by grafting a lactoside bearing an aldehyde-functionalized aglycone to the amino groups of chitosan or chitosan fiber followed by the enzymatic sialylation with sialyltransferase. The obtained water-soluble SL-chitosan conjugate bound HA with high affinity and inhibited effectively the viral attachment to host erythrocytes. Moreover, the SL-functionalized chitosan fiber efficiently removed the virus from an aqueous medium. The results collectively demonstrate that these potential new materials may function as the virus adsorbents for prevention and control of influenza. Importantly, these materials represent an appealing approach for presenting a protein ligand on a chitosan backbone, which is a versatile molecular platform for biofunctionalization and, thereby, can be used for not only antiviral designs, but also extensive medical development such as diagnosis and drug delivery.
摘要：
流感病毒的高传染性和基因变异性使设计有效的方法来控制感染尤其有挑战性。病毒表面的血凝素蛋白能借助结合于其糖原配体，如唾液酰乳糖，附着于宿主细胞表面。所以其成为抗病毒设计中非常有吸引力的靶目标。鉴于此，我们创造了容易构建和研发的两种基于脱乙酰壳多糖与唾液酰乳糖混合体的材料来实现抑制病毒粘附和净化的效果，一种水溶性聚合物或者是功能性纤维。这种合成通过移植一种以糖苷为骨架支撑的类似乙醛功能的糖苷配基到脱乙酰壳多糖或脱乙酰壳多糖纤维的氨基上面，然后用唾液酸转移酶进行唾液酰化作用。得到的水溶性的唾液酰乳糖与脱乙酰壳多糖的共轭物与血凝素具有很高的亲和性，可以有效的抑制病毒与宿主细胞的粘附。另外，具有唾液酰乳糖功能的脱乙酰壳多糖纤维能有效的移除水性媒介中的病毒。这些结果同时证实这些潜在的新材料可以起到病毒吸附剂的功效从而来预防和控制流感。重要的是，这些材料描绘了一种颇具吸引力的可以在脱乙酰壳多糖主链上提供一种蛋白配体的新方法，这种方法是可以实现生物功能的通用型分子平台，所以，这不仅可以用来抗病毒设计，也可以用于广泛的医疗研发，如诊断和药物输送。
