Characterization of the 8-hydroxyquinoline scaffold for inhibitors of West Nile virus serine protease
dc.contributor.author | Ezgimen, Manolya | |
dc.contributor.author | Lai, Huiguo | |
dc.contributor.author | Mueller, Niklaus H. | |
dc.contributor.author | Lee, Kyungae | |
dc.contributor.author | Cuny, Gregory D. | |
dc.contributor.author | Ostrov, David A. | |
dc.contributor.author | Padmanabhan, Radhakrishnan | |
dc.date.accessioned | 2020-03-10T17:31:23Z | |
dc.date.available | 2020-03-10T17:31:23Z | |
dc.date.issued | 2013-04 | |
dc.description.abstract | West Nile virus (WNV) is a mosquito-borne member of flaviviruses that causes significant morbidity and mortality especially among children. There is currently no approved vaccine or antiviral therapeutic for human use. In a previous study, we described compounds containing the 8-hydroxyquinoline (8-HQ) scaffold as inhibitors of WNV serine protease (NS2B/NS3pro) in a high throughput screen (HTS) using the purified WNV NS2B/NS3pro as the target. In this study, we analyzed potencies of some commercially available as well as chemically synthesized derivatives of 8-HQ by biochemical assays. An insight into the contribution of various substitutions of 8-HQ moiety for inhibition of the protease activity was revealed. Most importantly, the substitution of the N1 of the 8-HQ ring by –CH– in compound 26 significantly reduced the inhibition of the viral protease by this naphthalen-1-ol derivative. The kinetic constant (Ki) for the most potent 8-HQ inhibitor (compound 14) with an IC50 value of 2.01 ± 0.08 ?M using the tetra-peptide substrate was determined to be 5.8 ?M. This compound inhibits the WNV NS2B/NS3pro by a competitive mode of inhibition which is supported by molecular modeling. | |
dc.identifier.citation | Copyright 2012 Antiviral Research. This is a post-print version of a published paper that is available at: https://www.sciencedirect.com/science/article/pii/S0166354212000368. Recommended citation: Ezgimen, Manolya, Huiguo Lai, Niklaus H. Mueller, Kyungae Lee, Gregory Cuny, David A. Ostrov, and Radhakrishnan Padmanabhan. "Characterization of the 8-hydroxyquinoline scaffold for inhibitors of West Nile virus serine protease." Antiviral research 94, no. 1 (2012): 18-24. doi: 10.1016/j.antiviral.2012.02.003. This item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission. | |
dc.identifier.uri | https://hdl.handle.net/10657/5951 | |
dc.language.iso | en_US | |
dc.publisher | Antiviral Research | |
dc.subject | West Nile Virus protease inhibitors | |
dc.subject | Molecular modeling and docking | |
dc.subject | competitive inhibitors of West Nile vrius protease | |
dc.subject | Structure activity relationship study among 8 hydroxyquinoline derivatives | |
dc.title | Characterization of the 8-hydroxyquinoline scaffold for inhibitors of West Nile virus serine protease | |
dc.type | Article |