The conformational changes of Zika virus methyltransferase upon converting SAM to SAH

// Han Zhou 1, 2, * , Fenghua Wang 1, * , Haofeng Wang 1, * , Cheng Chen 1 , Tianqing Zhang 1 , Xu Han 1 , Deping Wang 1 , Chen Chen 1 , Chen Wu 1 , Wei Xie 1 , Zefang Wang 1 , Lei Zhang 1 , Lanfeng Wang 3 , Haitao Yang 1, 2 1 School of Life Sciences, Tianjin University, Tianjin 300072, China 2 Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin 300457, China 3 Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China * These authors contributed equally to this work Correspondence to: Haitao Yang, email: yanght@tju.edu.cn Lanfeng Wang, email: lanfwang@ips.ac.cn Keywords: Zika virus, methyltransferase, crystal structure, SAH, antiviral drug development Received: November 16, 2016      Accepted: January 11, 2017      Published: January 21, 2017 ABSTRACT An outbreak of Zika virus (ZIKV) infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly potentially associated with ZIKV infection has already caused a public health emergency of international concern. Currently, there are no clinically effective vaccines or antiviral drugs available to treat ZIKV infection. The methyltransferase domain (MTase) of ZIKV nonstructural protein 5 (NS5) can sequentially methylate guanine N-7 and ribose 2′-O to form m7N GpppA 2′Om cap structure in the new RNA transcripts. This methylation step is crucial for ZIKV replication cycle and evading the host immune system, making it a target for drug design. Here, we present the 1.76 A crystal structure of ZIKV MTase in complex with the byproduct SAH, providing insight into the elegant methylation process, which will benefit the following antiviral drug development.