Departamento de Química Orgánica, Facultad de Química , Universidad Complutense , 28040 Madrid , Spain.
Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ) , CSIC - Universidad de Sevilla , Av. Américo Vespucio 49 , Seville 41092 , Spain.
J Am Chem Soc. 2019 Sep 25;141(38):15403-15412. doi: 10.1021/jacs.9b08003. Epub 2019 Sep 11.
After the last epidemic of the Zika virus (ZIKV) in Brazil that peaked in 2016, growing evidence has been demonstrated of the link between this teratogenic flavivirus and microcephaly cases. However, no vaccine or antiviral drug has been approved yet. ZIKV and Dengue viruses (DENV) entry to the host cell takes place through several receptors, including dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), so that the blockade of this receptor through multivalent glycoconjugates supposes a promising biological target to inhibit the infection process. In order to get enhanced multivalency in biocompatible systems, tridecafullerenes appended with up to 360 1,2-mannobiosides have been synthesized using a strain-promoted cycloaddition of azides to alkynes (SPAAC) strategy. These systems have been tested against ZIKV and DENV infection, showing an outstanding activity in the picomolar range.
在巴西 2016 年爆发的寨卡病毒（ZIKV）最后一次疫情之后，越来越多的证据表明这种致畸性黄病毒与小头畸形病例之间存在关联。然而，目前还没有批准的疫苗或抗病毒药物。ZIKV 和登革热病毒（DENV）进入宿主细胞需要通过几种受体，包括树突状细胞特异性细胞间黏附分子-3 捕获非整联蛋白（DC-SIGN），因此通过多价糖缀合物阻断该受体是抑制感染过程的一个很有前途的生物靶点。为了在生物相容性系统中获得增强的多价性，已经使用叠氮化物与炔烃的应变促进环加成（SPAAC）策略合成了多达 360 个 1,2-甘露糖苷的十三倍富勒烯。这些系统已针对 ZIKV 和 DENV 感染进行了测试，在皮摩尔范围内表现出出色的活性。
