title: The crystal structure of Zika virus NS5 reveals conserved drug targets.
abstract: 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.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Duan
authors.affiliation: Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Song
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|College of Animal Sciences and Technology, Guangxi University, Nanning, China.
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chai
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.|College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Su
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China shiyi@im.ac.cn gaof@im.ac.cn.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.|Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.|Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China.
authors.forename: Yi
authors.identifier: 0000-0002-3053-2687
authors.initials: Y
authors.lastname: Shi
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China shiyi@im.ac.cn gaof@im.ac.cn.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.|Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.|Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China.|National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
authors.forename: George F
authors.identifier: 0000-0002-3869-615X
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism; D018360:Crystallography, X-Ray; D008780:Methyltransferases / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism*; D000071244:Zika Virus / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; C096041:NS5 protein, flavivirus; D017361:Viral Nonstructural Proteins; D008780:Methyltransferases; D012324:RNA-Dependent RNA Polymerase
keywords: RNA capping; Zika virus; crystal structure; methyltransferase; polymerase