Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Pharm Sci. 2011 Mar;100(3):831-5. doi: 10.1002/jps.22338. Epub 2010 Aug 25.
Effects of the commercial drug zanamivir (Relenza) covalently attached to poly-l-glutamine on the infectivity of influenza A viruses are examined using the plaque reduction assay and binding affinity to viral neuraminidase (NA). These multivalent drug conjugates exhibit (i) up to a 20,000-fold improvement in anti-influenza potency compared with the zanamivir parent against human and avian viral strains, including both wild-type and drug-resistant mutants, and (ii) superior neuraminidase (NA) inhibition constants, especially for the mutants. These findings provide a basis for exploring polymer-attached inhibitors as more efficacious therapeutics, particularly against drug-resistant influenza strains.
研究了共价连接到聚-L-谷氨酰胺上的商业药物扎那米韦（瑞乐沙）对流感 A 病毒感染力的影响，使用噬斑减少测定法和与病毒神经氨酸酶（NA）的结合亲和力来检测。这些多价药物缀合物表现出（i）与扎那米韦母体相比，对人类和禽源病毒株（包括野生型和耐药突变体）的抗流感效力提高了多达 20,000 倍，（ii）对神经氨酸酶（NA）的抑制常数更高，尤其是对突变体。这些发现为探索聚合物连接抑制剂作为更有效的治疗药物提供了依据，特别是针对耐药性流感株。
