McKimm-Breschkin Jennifer L, Barrett Susan
CSIRO Manufacturing, 343 Royal Parade, Parkville, 3052, Australia.
Antiviral Res. 2015 Feb;114:62-6. doi: 10.1016/j.antiviral.2014.12.004. Epub 2014 Dec 9.
The neuraminidase (NA) inhibitors oseltamivir and zanamivir are administered twice daily for 5days for treatment of influenza. Laninamivir is a 7-methoxy derivative of zanamivir, but a single dose is effective when taken as the laninamivir octanoate prodrug. We show here in IC50 kinetics assays and a solid phase reactivation assay that compared to zanamivir laninamivir also demonstrates slow binding to but slower dissociation from multiple wild type NAs. A D197E mutation in an influenza B and an E119G in an N9 neuraminidase which confer 15- and 150-fold resistance to laninamivir result in faster binding and dissociation. Despite similar IC50s our assays demonstrate more rapid dissociation of laninamivir from clade 1 compared to 2 H5N1 NAs.
神经氨酸酶（NA）抑制剂奥司他韦和扎那米韦用于流感治疗时需每日服用两次，持续5天。拉尼米韦是扎那米韦的7 - 甲氧基衍生物，但作为拉尼米韦辛酸酯前药服用时单剂量即有效。我们在此通过IC50动力学测定和固相再活化测定表明，与扎那米韦相比，拉尼米韦与多种野生型NA的结合缓慢但解离更慢。乙型流感中的D197E突变和N9神经氨酸酶中的E119G突变分别对拉尼米韦产生15倍和150倍的耐药性，导致结合和解离更快。尽管IC50相似，但我们的测定表明，与2型H5N1 NA相比，拉尼米韦从1型H5N1 NA的解离更快。
