Predicting Zika virus structural biology: Challenges and opportunities for intervention
Predicting Zika virus structural biology: Challenges and opportunities for intervention
复制标题
DOI：
10.1177/2040206616653873
复制
发表时间：
2015-08-01
影响因子：
--
通讯作者：
Schinazi, Raymond F.
中科院分区：
文献类型：
--
作者：
Cox, Bryan D.;Stanton, Richard A.;Schinazi, Raymond F.
寨卡病毒是一种新兴的危机，因为感染与严重的神经系统疾病、格林-巴利综合征和胎儿小头畸形有关。寨卡病毒感染的原因有哪些？这种病毒是黄病毒属的一部分，与登革热病毒、西尼罗河病毒和日本脑炎病毒密切相关。与其他黄病毒一样，寨卡病毒基因组编码三种结构蛋白（衣壳、前体膜和包膜）和七种非结构蛋白（NS 1、NS 2A、NS 2B、NS 3、NS 4A、NS 4 B和NS 5）。目前，没有结构信息存在于这些病毒蛋白，以促进疫苗设计和合理的药物discovery.Methods结构的所有寨卡病毒蛋白进行了预测，使用实验模板，从密切相关的病毒使用在线SwissModel服务器。使用Visual Molecular Dynamics Multiseq软件将这些同源性模型与来自其他病毒的药物靶标进行比较。序列比对的所有寨卡病毒多聚蛋白进行使用Clustal欧米茄，以确定在特定的病毒蛋白的突变牵连pathogenicity.Results的前体膜，包膜，和NS 1蛋白是独特的寨卡病毒突出疫苗设计可能面临的挑战。寨卡病毒株之间的序列差异发生在前体膜、包膜、NS 2A、NS 3、NS 4 B和NS 5上的关键位置，这些位置是差异致病的潜在位点。登革热病毒和西尼罗河病毒NS 3和NS 5中的可药用口袋保留在预测的Zika病毒structure.Conclusions铅候选人Zika病毒可能会建立使用NS 3和NS 5抑制剂从其他黄病毒，和结构可以提供机会，寨卡病毒的干预策略。
Background Zika virus is an emerging crisis as infection is implicated in severe neurological disordersGuillain-Barre syndrome and fetal microcephaly. There are currently no treatment options available for Zika virus infection. This virus is part of the flavivirus genus and closely related to Dengue Fever Virus, West Nile Virus, and Japanese Encephalitis Virus. Like other flaviviruses, the Zika virus genome encodes three structural proteins (capsid, precursor membrane, and envelope) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). Currently, no structural information exists on these viral proteins to facilitate vaccine design and rational drug discovery.Methods Structures for all Zika virus viral proteins were predicted using experimental templates available from closely related viruses using the online SwissModel server. These homology models were compared to drug targets from other viruses using Visual Molecular Dynamics Multiseq software. Sequential alignment of all Zika virus polyproteins was performed using Clustal Omega to identify mutations in specific viral proteins implicated in pathogenesis.Results The precursor membrane, envelope, and NS1 proteins are unique to Zika virus highlighting possible challenges in vaccine design. Sequential differences between Zika virus strains occur at critical positions on precursor membrane, envelope, NS2A, NS3, NS4B, and NS5 as potential loci for differential pathogenesis. Druggable pockets in Dengue Fever Virus and West Nile Virus NS3 and NS5 are retained in predicted Zika virus structures.Conclusions Lead candidates for Zika virus can likely be established using NS3 and NS5 inhibitors from other flaviviruses, and the structures presented can provide opportunities for Zika virus intervention strategies.