Please use this identifier to cite or link to this item: https://doi.org/10.1002/cmdc.201300244
Title: Synthesis and in vitro evaluation of west nile virus protease inhibitors based on the 1,3,4,5-tetrasubstituted 1H-Pyrrol-2(5H)-one scaffold
Authors: Gao, Y.
Samanta, S.
Cui, T.
Lam, Y. 
Keywords: Antiviral agents
Bioorganic chemistry
Docking studies
Inhibitors
NS2B-NS3 protease
Issue Date: Sep-2013
Source: Gao, Y., Samanta, S., Cui, T., Lam, Y. (2013-09). Synthesis and in vitro evaluation of west nile virus protease inhibitors based on the 1,3,4,5-tetrasubstituted 1H-Pyrrol-2(5H)-one scaffold. ChemMedChem 8 (9) : 1554-1560. ScholarBank@NUS Repository. https://doi.org/10.1002/cmdc.201300244
Abstract: West Nile virus (WNV), a member of the Flaviviridae family, is a mosquito-borne pathogen that causes a large number of human infections each year. There are currently no vaccines or antiviral therapies available for human use against WNV. Therefore, efforts to develop new chemotherapeutics against this virus are highly desired. In this study, a WNV NS2B-NS3 protease inhibitor with a 1,3,4,5-tetrasubstituted 1H-pyrrol-2(5H)-one scaffold was identified by screening a small library of nonpeptidic compounds. Optimization of this initial hit by the synthesis and screening of a focused library of compounds with this scaffold led to the identification of a novel uncompetitive inhibitor ((-)-1a16, IC50=2.2±0.7μM) of the WNV NS2B-NS3 protease. Molecular docking of the chiral compound onto the WNV protease indicates that the Renantiomer of 1a16 interferes with the productive interactions between the NS2B cofactor and the NS3 protease domain and is thus the preferred isomer for inhibition of the WNV NS2B-NS3 protease. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Source Title: ChemMedChem
URI: http://scholarbank.nus.edu.sg/handle/10635/95068
ISSN: 18607179
DOI: 10.1002/cmdc.201300244
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