Zika Virus Protease: An Antiviral Drug Target

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Zika Virus Protease: An Antiviral Drug Target
Zika Virus Protease: An Antiviral Drug Target
Other Titles:
Trends in Microbiology
Publication Date:
05 August 2017
Zika Virus Protease: An Antiviral Drug Target Kang, CongBao et al. Trends in Microbiology , Volume 25 , Issue 10 , 797 - 808
The recent outbreak of Zika virus (ZIKV) infection has caused global concern due to its link to severe damage to the brain development of foetuses and neuronal complications in adult patients. A worldwide research effort has been undertaken to identify effective and safe treatment and vaccination options. Among the proposed viral and host components, the viral NS2B-NS3 protease represents an attractive drug target due to its essential role in the virus life cycle. Here, we outline recent progress in studies on the Zika protease. Biochemical, biophysical and structural studies on different protease constructs provide new insight into the structure and activity of the protease. The unlinked construct displays higher enzymatic activity and better mimics the native state of the enzyme and therefore is better suited for drug discovery. Furthermore, the structure of the free enzyme adopts a closed conformation and a preformed active site. The availability of biophysical data for a fragment hit and peptide inhibitors, as well as the attainability of soakable crystals suggest that the unlinked construct is a promising tool for drug discovery.
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Funding Info:
(1) a start-up grant from Lee Kong Chian School of Medicine, Nanyang Technological University, (2) National Medical Research Council grant CBRG15May045, (3) National Research Foundation grant NRF2016NRF-CRP001-063 to D.L. (4) A*STAR JCO grant (1431AFG102/1331A028) to C.K.
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