Zika virus proteins at an atomic scale: how does structural biology help us to understand and develop vaccines and drugs against Zika virus infection?
Zika virus proteins at an atomic scale: how does structural biology help us to understand and develop vaccines and drugs against Zika virus infection?
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DOI：
10.1590/1678-9199-jvatitd-2019-0013
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发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
Moraes, Adolfo Henrique
中科院分区：
文献类型：
--
作者：
Valente, Ana Paula;Moraes, Adolfo Henrique
在巴西和其他热带地区，寨卡病毒感染与母亲在怀孕期间感染的新生儿小头畸形和成人格林-巴利综合征等临床并发症直接相关。最近，研究的重点是开发新的疫苗和候选药物来对抗寨卡病毒感染，因为这些都不是可用的。为了促进疫苗和药物的开发工作，了解寨卡病毒识别、感染和阻断的分子基础变得重要。为此，寨卡病毒蛋白的结构测定至关重要。寨卡病毒基因组测序鉴定出10种蛋白质，分别是3种结构蛋白(蛋白E、蛋白C和蛋白PrM)和7种非结构蛋白(NS1、NS2A、NS2B、NS3、NS4A、NS4B和NS5)。总之，这些蛋白质是药物和抗体识别的主要目标。在这里，我们考察了寨卡病毒高分辨率结构生物学的新发现，观察了通过X射线结晶学、核磁共振光谱和低温电子显微镜等最先进的结构方法确定的寨卡病毒蛋白质的相互作用和功能。本研究的目的是有助于在原子水平上理解寨卡病毒感染的结构基础，并指出与其他黄病毒的异同。
In Brazil and in other tropical areas Zika virus infection was directly associated with clinical complications as microcephaly in newborn children whose mothers were infected during pregnancy and the Guillain-Barre syndrome in adults. Recently, research has been focused on developing new vaccines and drug candidates against Zika virus infection since none of those are available. In order to contribute to vaccine and drug development efforts, it becomes important the understanding of the molecular basis of the Zika virus recognition, infection and blockade. To this purpose, it is essential the structural determination of the Zika virus proteins. The genome sequencing of the Zika virus identified ten proteins, being three structural (protein E, protein C and protein prM) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). Together, these proteins are the main targets for drugs and antibody recognition. Here we examine new discoveries on high-resolution structural biology of Zika virus, observing the interactions and functions of its proteins identified via state-of-art structural methodologies as X-ray crystallography, nuclear magnetic resonance spectroscopy and cryogenic electronic microscopy. The aim of the present study is to contribute to the understanding of the structural basis of Zika virus infection at an atomic level and to point out similarities and differences to others flaviviruses