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dc.contributor.authorQuek, Jun Pingen_US
dc.contributor.authorLiu, Shuangen_US
dc.contributor.authorZhang, Zhenzhenen_US
dc.contributor.authorLi, Yanen_US
dc.contributor.authorNg, Elizabeth Yihuien_US
dc.contributor.authorLoh, Ying Ruen_US
dc.contributor.authorHung, Alvin W.en_US
dc.contributor.authorLuo, Dahaien_US
dc.contributor.authorKang, CongBaoen_US
dc.identifier.citationQuek, J. P., Liu, S., Zhang, Z., Li, Y., Ng, E. Y., Loh, Y. R., . . . Kang, C. (2020). Identification and structural characterization of small molecule fragments targeting Zika virus NS2B-NS3 protease. Antiviral Research, 175, 104707-. doi:10.1016/j.antiviral.2020.104707en_US
dc.description.abstractZika virus (ZIKV) NS2B-NS3 protease is a validated antiviral target as it is essential for maturation of viral proteins. However, its negatively charged active site hinders the development of orthosteric small-molecule inhibitors. Fragment-based drug discovery (FBDD) is a powerful tool to generate novel chemical starting points against difficult drug targets. In this study, we scre ened a fragment compound library against the Zika protease using a primary thermal shift assay and identified twenty-two fragments which (bind to and) stabilize the protease. We then determined the X-ray crystal structures of two hits from different classes, all of which bind to the S1 pocket of the protease. We confirmed that these two fragments bind to the protease without inducing significant conformational changes using solution NMR spectroscopy. These fragment scaffolds serve as the starting point for subsequent lead compound development.en_US
dc.description.sponsorshipNRF (Natl Research Foundation, S’pore)en_US
dc.description.sponsorshipNMRC (Natl Medical Research Council, S’pore)en_US
dc.description.sponsorshipMOH (Min. of Health, S’pore)en_US
dc.relation.ispartofAntiviral Researchen_US
dc.rights© 2020 Elsevier B.V. All rights reserved. This paper was published in Antiviral Research and is made available with permission of Elsevier B.V.en_US
dc.titleIdentification and structural characterization of small molecule fragments targeting Zika virus NS2B-NS3 proteaseen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.organizationNTU Institute of Structural Biologyen_US
dc.contributor.research4G Research Laben_US
dc.description.versionAccepted versionen_US
dc.subject.keywordsZika Virusen_US
dc.subject.keywordsFragment-based Drug Discoveryen_US
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