Departments of Pediatrics, Weill Medical College of Cornell University, New York, New York 10021, USA. (
J Infect Dis. 2010 Jul 15;202(2):234-41. doi: 10.1086/653621.
The first step in infection by human parainfluenza viruses (HPIVs) is binding to the surface of respiratory epithelial cells via interaction between viral receptor-binding molecules and sialic acid-containing receptors. DAS181, a recombinant sialidase protein containing the catalytic domain of Actinomyces viscosus sialidase, removes cell surface sialic acid, and we proposed that it would inhibit HPIV infection.
Depletion of sialic acid receptors by DAS181 was evaluated by lectin-binding assays. Anti-HPIV activity in cultured cell lines and in human airway epithelium was assessed by the reduction in viral genomes and/or plaque forming units on treatment. In vivo efficacy of intranasally administered DAS181 was assessed using a cotton rat model.
DAS181-mediated desialylation led to anti-HPIV activity in cell lines and human airway epithelium. Intranasal DAS181 in cotton rats, a model for human disease, significantly curtailed infection.
Enzymatic removal of the sialic acid moiety of HPIV receptors inhibits infection with all tested HPIV strains, both in vitro and in cotton rats. Enzyme-mediated removal of sialic acid receptors represents a novel antiviral strategy for HPIV. The results of this study raise the possibility of a broad spectrum antiviral agent for influenza virus and HPIVs.
人类副流感病毒（HPIVs）感染的第一步是通过病毒受体结合分子与含有唾液酸的受体之间的相互作用，结合到呼吸道上皮细胞的表面。DAS181 是一种含有粘膜炎放线菌唾液酸酶催化结构域的重组唾液酸酶蛋白，可去除细胞表面的唾液酸，我们推测它会抑制 HPIV 感染。
通过凝集素结合试验评估 DAS181 对唾液酸受体的消耗。通过处理后病毒基因组和/或蚀斑形成单位的减少，评估 DAS181 在培养的细胞系和人呼吸道上皮中的抗 HPIV 活性。通过棉鼠模型评估鼻内给予 DAS181 的体内疗效。
DAS181 介导的脱唾液酸化导致细胞系和人呼吸道上皮中的抗 HPIV 活性。在棉鼠（一种人类疾病的模型）中，鼻内给予 DAS181 可显著抑制感染。
HPIV 受体唾液酸部分的酶促去除抑制了所有测试的 HPIV 株的感染，无论是在体外还是在棉鼠中。酶介导的唾液酸受体去除代表了一种针对 HPIV 的新型抗病毒策略。本研究的结果提出了一种针对流感病毒和 HPIVs 的广谱抗病毒药物的可能性。
