Rational design of a flavivirus vaccine through abolishing 1 viral RNA 2 ′ - O methylation
نویسندگان
چکیده
8 Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 9 100071, China; State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, 10 China; Novartis Institute for Tropical Diseases, Singapore; Center for Biomaterials 11 and Biopathways, Department of Chemistry, Zhejiang University, Hangzhou 310027, 12 China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese 13 Academy of Science, Wuhan 430071, China; Shanghai Institute for Pasteur, Chinese 14 Academy of Science, Shanghai, China; Singapore Immunology Network, ASTAR 15 (Agency for Science, Technology and Research), Singapore 16
منابع مشابه
Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation.
Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2'-O cap of their RNA; alternatively, they "snatch" host mRNA cap to form the 5' end of viral RNA. The function of 2'-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmi...
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Flaviviruses encode a single methyltransferase domain that sequentially catalyzes two methylations of the viral RNA cap, GpppA-RNA-->m(7)GpppA-RNA-->m(7)GpppAm-RNA, by using S-adenosyl-l-methionine (SAM) as a methyl donor. Crystal structures of flavivirus methyltransferases exhibit distinct binding sites for SAM, GTP, and RNA molecules. Biochemical analysis of West Nile virus methyltransferase ...
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RNA modification plays an important role in modulating host-pathogen interaction. Flavivirus NS5 protein encodes N-7 and 2'-O methyltransferase activities that are required for the formation of 5' type I cap (m(7)GpppAm) of viral RNA genome. Here we reported, for the first time, that flavivirus NS5 has a novel internal RNA methylation activity. Recombinant NS5 proteins of West Nile virus and De...
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Dengue virus (DENV) causes several hundred million human infections and more than 20,000 deaths annually. Neither an efficacious vaccine conferring immunity against all four circulating serotypes nor specific drugs are currently available to treat this emerging global disease. Capping of the DENV RNA genome is an essential structural modification that protects the RNA from degradation by 5' exo...
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The flavivirus methyltransferase (MTase) sequentially methylates the N7 and 2'-O positions of the viral RNA cap (GpppA-RNA → m(7)GpppA-RNA → m(7)GpppAm-RNA), using S-adenosyl-l-methionine (AdoMet) as a methyl donor. We report here that sinefungin (SIN), an AdoMet analog, inhibits several flaviviruses through suppression of viral MTase. The crystal structure of West Nile virus MTase in complex w...
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