Structural biology and drug discovery targeting Zika virus proteins

抄録

Zika fever is an infectious disease caused by the Zika virus (ZIKV) of the Flaviviridae family. The typical symptoms post-infection are mild fever, rash, arthralgia, headache and conjunctivitis, similar though less intense, to the symptoms of dengue. Originally described in 1947 in Africa, the disease was sparsely observed in other countries over 50 years, until outbreaks were observed in Micronesia (2007) and French Polynesia (2013). It was only when the disease reached Brazil in 2015, with a major outbreak followed by the spread throughout the Americas and other continents, that the association of Zika virus (ZIKV) infections with severe neurological complications, including microcephaly and other congenital disorders in newborns and Guillain-Barré syndrome in adults, was identified. The lack of an effective vaccine or therapeutic treatment, lead to international efforts towards the understanding of the molecular determinants of ZIKV infection, transmission and pathology. We will describe our structural biology studies of Zika virus proteins, including the crystallographic structures of NS5 RNA-dependent RNA polymerase and NS3-helicase, and the ensuing efforts towards the identification on inhibitors and development of novel antiviral lead candidates.