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Structural basis of Zika virus methyltransferase inhibition by sinefungin

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Abstract

Zika virus is considered a major global threat to human kind. Here, we present a crystal structure of one of its essential enzymes, the methyltransferase, with the inhibitor sinefungin. This structure, together with previously solved structures with bound substrates, will provide the information needed for rational inhibitor design. Based on the structural data we suggest the modification of the adenine moiety of sinefungin to increase selectivity and to covalently link it to a GTP analogue, to increase the affinity of the synthesized compounds.

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Acknowledgements

The Project was also supported by Project InterBioMed LO1302 from Ministry of Education of the Czech Republic, the support of the Academy of Sciences of the Czech Republic (RVO: 61388963) is also acknowledged.

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  1. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic

    Kamil Hercik, Jiri Brynda, Radim Nencka & Evzen Boura

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  1. Kamil Hercik
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Correspondence to Radim Nencka or Evzen Boura.

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Hercik, K., Brynda, J., Nencka, R. et al. Structural basis of Zika virus methyltransferase inhibition by sinefungin. Arch Virol 162, 2091–2096 (2017). https://doi.org/10.1007/s00705-017-3345-x

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  • DOI: https://doi.org/10.1007/s00705-017-3345-x

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