Structural Biology of the Zika Virus

Zika virus (ZIKV), a Flaviviridae family member transmitted to humans by mosquitoes, has emerged as a major health concern. ZIKV infections can cause serious neurological complications in adults, and infection in pregnant women can cause congenital malformations, including fetal and newborn microcephaly. In response to this emerging concern, the structural virology field was quick to explore the features of ZIKV. These efforts have provided significant insights into ZIKV pathogenesis, and have identified targets for drug design. Here, we review the remarkable progress in structure-based ZIKV research and discuss the current challenges and future opportunities. Cryo-electron microscopy (EM) structural studies revealed that the ZIKV particle has two unique features: a protruding N154 glycosylation site and a more compact surface with higher thermostability. Moreover, the immature ZIKV contains a partially ordered capsid protein shell, which is lacking in the mature ZIKV particle, suggesting a rearrangement of capsid shell during maturation. Both flavivirus E-cross-reactive and ZIKV E-specific neutralizing antibodies confer protection against ZIKV infection in a mouse model, and structural analysis showed that these antibodies bind to different regions on the E protein. Analysis of the structure of the full-length ZIKV NS1 identified a new membrane-association site in the wing domain, and unique characteristics of its outer surface. Analysis of the structures of ZIKV NS3 and NS5 revealed conserved features that will aid in the structure-based design of antiviral compounds against ZIKV.