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Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor

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Science  07 Jul 2016:
aag2419
DOI: 10.1126/science.aag2419

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  • RE: “Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor”
    • Qiuyun Liu, Superviser/writting/Professor, State Key Laboratory of Biocontrol, MOE Key Laboratory of Aquatic Product Safety, Sun Yat-sen University, China
    • Other Contributors:
      • Jianguo He, Writting/Professor, State Key Laboratory of Biocontrol, MOE Key Laboratory of Aquatic Product Safety, Sun Yat-sen University, China
      • Shaoping Weng, Writting/Professor, State Key Laboratory of Biocontrol, MOE Key Laboratory of Aquatic Product Safety, Sun Yat-sen University, China
      • Ying Zhang, Writting/Research Associate, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China
      • Jing Li, Writting/Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Jingli Peng, Writting/Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Li Xu, Writting/Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China

    High leucine content in the polyprotein of Zika virus may contribute to neurotropism

    Besides the tertiary structure, the primary sequences of the Zika viral proteins are also concerns for viral infections and virulence. Leucines accounted for 9.144% of the polyprotein of Zika virus with a primary sequence of 3423 amino acids (GenBank accession no. KJ776791). Leucine possesses two delta methyl groups, and the hyperconjugation in the distal end of the side group enables intermolecular interactions via van der Waals forces in conjunction with hydrophobic forces. This assumption is supported by bond lengths (1), NMR chemical shifts (2-3) and reports of leucine zipper motifs facilitating dimerization (4).
    The amino acid residue lacks γ methyl group, thus devoid of the σ-σ hyperconjugation in beta carbon. Consequently the side group lacks strong van der Waals interactions with the carbonyl group of leucine. This results in the weak secondary chemical bonding and low cation affinities with the carbonyl oxygen, corroborated by the chemical shift anisotropy of σ22 element of the tensor and short bond lengths of carbonyl carbon with carbonyl oxygen (5-6). The changed ion homeostasis leads to subnormal osmolarity, and the protein and degraded peptides would affect the development of the brain resulting in microcephaly. Proteins rich in leucine and basic amino acids may be damaging to cells (7-8). The leucine content is around 15% in the virulence protein VP24 of Ebola vi...

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    Competing Interests: None declared.