Zika virus protease : an antiviral drug target
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 op...
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sg-ntu-dr.10356-1407862020-11-01T05:16:35Z Zika virus protease : an antiviral drug target Kang, CongBao Keller, Thomas H. Luo, Dahai Lee Kong Chian School of Medicine (LKCMedicine) NTU Institute of Structural Biology Science::Medicine Flavivirus Protease Inhibitor 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 a lead 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. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) NMRC (Natl Medical Research Council, S’pore) Accepted version 2020-06-02T03:31:43Z 2020-06-02T03:31:43Z 2017 Journal Article Kang, C., Keller, T. H., & Luo, D. (2017). Zika virus protease : an antiviral drug target. Trends in Microbiology, 25(10), 797-808. doi:10.1016/j.tim.2017.07.001 0966-842X https://hdl.handle.net/10356/140786 10.1016/j.tim.2017.07.001 28789826 2-s2.0-85026819700 10 25 797 808 en Trends in Microbiology © 2017 Elsevier Ltd. All rights reserved. This paper was published in Trends in Microbiology and is made available with permission of Elsevier Ltd. application/pdf |
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Science::Medicine Flavivirus Protease Inhibitor Kang, CongBao Keller, Thomas H. Luo, Dahai Zika virus protease : an antiviral drug target |
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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 a lead 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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Lee Kong Chian School of Medicine (LKCMedicine) |
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Lee Kong Chian School of Medicine (LKCMedicine) Kang, CongBao Keller, Thomas H. Luo, Dahai |
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Article |
author |
Kang, CongBao Keller, Thomas H. Luo, Dahai |
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Kang, CongBao |
title |
Zika virus protease : an antiviral drug target |
title_short |
Zika virus protease : an antiviral drug target |
title_full |
Zika virus protease : an antiviral drug target |
title_fullStr |
Zika virus protease : an antiviral drug target |
title_full_unstemmed |
Zika virus protease : an antiviral drug target |
title_sort |
zika virus protease : an antiviral drug target |
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2020 |
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https://hdl.handle.net/10356/140786 |
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1683493411567435776 |