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The crystal structure of Zika virus NS 5 reveals conserved drug targets
Author(s) -
Duan Wenqian,
Song Hao,
Wang Haiyuan,
Chai Yan,
Su Chao,
Qi Jianxun,
Shi Yi,
Gao George F
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201696241
Subject(s) - biology , zika virus , virology , virus , genetics , computational biology
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, NS 5 plays key roles in the life cycle and survival of the virus through its N‐terminal methyltransferase ( MT ase) and C‐terminal RNA ‐dependent RNA polymerase (RdRp) domains. Here, we present the crystal structures of ZIKV NS 5 MT ase in complex with an RNA cap analogue ( m7 GpppA) and the free NS 5 RdRp. We have identified the conserved features of ZIKV NS 5 MT ase 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 .