Crystal structure of zika virus ns2b-ns3 protease in complex with a boronate inhibitor

Jian Lei, Guido Hansen, Christoph Nitsche, Christian D. Klein, Linlin Zhang, Rolf Hilgenfeld*

*Corresponding author for this work
59 Citations (Scopus)


The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target.The 2.7 angstrom crystal structure of ZIKV protease in complex with a peptidomimetic boronic acid inhibitor reveals a cyclic diester between the boronic acid and glycerol. The P2 4- Aminomethylphenylalanine moiety of the inhibitor forms a salt-bridge with the nonconserved Asp83 of NS2B; ion-pairing between Asp83 and the P2 residue of the substrate likely accounts for the enzyme's high catalytic efficiency. The unusual dimer of the ZIKV protease:inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing.

Original languageEnglish
Issue number6298
Pages (from-to)503-505
Number of pages3
Publication statusPublished - 29.07.2016


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