Preparation of a thioxoimidazolidin-linked sialoside BSA conjugate for the inhibition of influenza virus

IF 2.4 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Carbohydrate Research Pub Date : 2024-10-09 DOI:10.1016/j.carres.2024.109287

Haijuan Qin , Zhiwei Huang , Xue Mi , Shuai Zhang , Han-Yu Liu , Jia-Ning Wang , Mingming Xue , Zhiqi Lao , Yang Yang

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Abstract

A novel thioxoimidazolidin-linked sialoside bovine serum albumin (WM-BSA) conjugate was synthesized and evaluated as an inhibitor of influenza virus hemagglutinin (HA) and neuraminidase (NA). The multivalent conjugate was prepared by the attachment of thioxoimidazolidin-sialoside monomer (WM) to BSA via adipate linker. Surface plasmon resonance analysis revealed that WM-BSA exhibited potent binding to recombinant influenza HA and NA proteins, with dissociation constants in the submicromolar range. WM-BSA also demonstrated inhibitory activities in the low micromolar range against HA and NA proteins from multiple influenza strains. Investigation of cytopathic effects in infected MDCK cells indicated that WM-BSA possessed antiviral activity with EC₅₀ values of 35–55 μM. The multivalent presentation of sialosides on the BSA scaffold significantly enhanced both the binding affinity and degree of inhibition compared to the monomeric compound WM. These results demonstrate the potential of multivalent sialoside-protein conjugate as a platform for developing novel anti-influenza agent.

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制备用于抑制流感病毒的硫代咪唑烷连硅糖苷 BSA 结合物

研究人员合成了一种新型硫代咪唑啉连接的硅糖苷牛血清白蛋白（WM-BSA）共轭物，并将其作为流感病毒血凝素（HA）和神经氨酸酶（NA）的抑制剂进行了评估。这种多价共轭物是通过己二酸酯连接体将硫代咪唑烷-苷单体（WM）连接到 BSA 上制备而成的。表面等离子共振分析表明，WM-BSA 与重组流感 HA 和 NA 蛋白的结合力很强，解离常数在亚摩尔范围内。WM-BSA 还对多种流感病毒株的 HA 和 NA 蛋白具有低微摩尔范围的抑制活性。对受感染的 MDCK 细胞进行的细胞病理效应研究表明，WM-BSA 具有抗病毒活性，其 EC50 值为 35-55 μM。与单体化合物 WM 相比，在 BSA 支架上多价呈现的硅苷大大提高了结合亲和力和抑制程度。这些结果表明，多价硅藻糖苷-蛋白共轭物具有开发新型抗流感药物平台的潜力。

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来源期刊

Carbohydrate Research 化学-生化与分子生物学

CiteScore

5.00

自引率

3.20%

发文量

183

审稿时长

3.6 weeks

期刊介绍： Carbohydrate Research publishes reports of original research in the following areas of carbohydrate science: action of enzymes, analytical chemistry, biochemistry (biosynthesis, degradation, structural and functional biochemistry, conformation, molecular recognition, enzyme mechanisms, carbohydrate-processing enzymes, including glycosidases and glycosyltransferases), chemical synthesis, isolation of natural products, physicochemical studies, reactions and their mechanisms, the study of structures and stereochemistry, and technological aspects. Papers on polysaccharides should have a "molecular" component; that is a paper on new or modified polysaccharides should include structural information and characterization in addition to the usual studies of rheological properties and the like. A paper on a new, naturally occurring polysaccharide should include structural information, defining monosaccharide components and linkage sequence. Papers devoted wholly or partly to X-ray crystallographic studies, or to computational aspects (molecular mechanics or molecular orbital calculations, simulations via molecular dynamics), will be considered if they meet certain criteria. For computational papers the requirements are that the methods used be specified in sufficient detail to permit replication of the results, and that the conclusions be shown to have relevance to experimental observations - the authors'' own data or data from the literature. Specific directions for the presentation of X-ray data are given below under Results and "discussion".