The crystal structure of Zika virus NS5 reveals conserved drug targets
-
Wenqian Duan [1] ; Hao Song [1] ; Haiyuan Wang [1] ; Yan Chai [1] ; Chao Su [1] ; Jianxun Qi [1] ; Yi Shi [1] ; George F Gao [1]
-
[1] Chinese Academy of Sciences
Chinese Academy of Sciences
China
-
- Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 7, 2017, págs. 919-933
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
-
Resumen
Zika virus (ZIKV) has emerged as major health concern, as ZIKV infection has been shown to be associated with microcephaly, severe neurological disease and possibly male sterility. As the largest protein component within the ZIKV replication complex, NS5 plays key roles in the life cycle and survival of the virus through its N‐terminal methyltransferase (MTase) and C‐terminal RNA‐dependent RNA polymerase (RdRp) domains. Here, we present the crystal structures of ZIKV NS5 MTase in complex with an RNA cap analogue (m7GpppA) and the free NS5 RdRp. We have identified the conserved features of ZIKV NS5 MTase and RdRp structures that could lead to development of current antiviral inhibitors being used against flaviviruses, including dengue virus and West Nile virus, to treat ZIKV infection. These results should inform and accelerate the structure‐based design of antiviral compounds against ZIKV.
