Preventing Influenza A Virus Infection by Mixed Inhibition of Neuraminidase and Hemagglutinin by Divalent Inhibitors
作者:Xuan Wei、Wenjuan Du、Margherita Duca、Guangyun Yu、Erik de Vries、Cornelis A. M. de Haan、Roland J. Pieters
DOI:10.1021/acs.jmedchem.2c00319
日期:2022.5.26
Divalentinhibitors of the neuraminidase enzyme (NA) of the Influenza A virus were synthesized with vastly different spacers. The spacers varied from 14 to 56 atoms and were relatively rigid by way of the building blocks and their connection by CuAAC. As the ligand for these constructs, a Δ4-β-d-glucoronide was used, which can be prepared form N-acetyl glucosamine. This ligand showed good NA inhibitory
甲型流感病毒的神经氨酸酶 (NA) 的二价抑制剂是用截然不同的间隔物合成的。间隔物从 14 到 56 个原子不等,并且通过构建块及其通过 CuAAC 的连接而相对刚性。作为这些构建体的配体,使用Δ 4 -β- d -葡糖苷酸,其可以由N-乙酰氨基葡糖制备。该配体显示出良好的 NA 抑制效力,但具有通过多价增强改进的空间。合成的化合物在 NA 活性测定中显示出适度的效力增强,但在 4 天的细胞病变效应测定中显示出相当大的效力增加。除了 NA 外,这些化合物还可以抑制血凝素的证明可能是增强的原因。