We report the synthesis of multivalent oleanolic acid (OA) protein conjugates as nonglycosylated neomucin mimic for the capture and entry inhibition of influenza viruses. Oleanolic acid derivatives bearing an amine-terminated linker were synthesized by esterification of carboxylic acid and further grafted onto the human serum albumin (HSA) via diethyl squarate method. The binding of hemagglutinin (HA) on the virion surface to the synthetic neomucin was evaluated by hemagglutination inhibition assay. The influenza virus capture ability of the PEGylated OA-HSA conjugate was further investigated by Dynamic Light Scattering (DLS), virus capture assay and Isothermal Titration Calorimeter (ITC) techniques. The pronounced agglutination of viral particles, the high capture efficiency and affinity constant indicate that this neoprotein is comparable to natural glycosylated mucin, suggesting that this material could potentially be used as anti-infective barriers to prevent virus from invading host cells. The study also rationalizes the feasibility of antiviral drug development based on OA or other antiviral small molecules conjugated protein strategies.

我们报告了多价齐墩果酸（OA）蛋白共轭物的合成，作为非糖基化的新粘蛋白模拟物，用于捕获和抑制流感病毒。通过羧酸的酯化反应合成带有胺端基连接基的齐墩果酸衍生物，然后通过以下方法将其接枝到人血清白蛋白（HSA）上方酸二乙酯法。通过血凝抑制测定法评价病毒体表面上的血凝素（HA）与合成新粘蛋白的结合。通过动态光散射（DLS），病毒捕获测定法和等温滴定热量计（ITC）技术进一步研究了聚乙二醇化OA-HSA缀合物对流感病毒的捕获能力。病毒颗粒的明显凝集，高捕获效率和亲和常数表明，该新蛋白与天然糖基化粘蛋白相当，表明该材料可能被用作抗感染屏障，以防止病毒入侵宿主细胞。该研究还合理化了基于OA或其他抗病毒小分子结合蛋白策略的抗病毒药物开发的可行性。