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Yellow fever virus NS3 protease: peptide-inhibition studies.

Loehr, Kristina and Knox, John and Phong, Wai Yee and Ma, Ngai Ling and Yin, Zheng and Sampath, Aruna and Patel, Sejal and Wang, Wei and Chan, Wai Ling and Rao, Ranga and Wang, Gang and Vasudevan, Subhash and Keller, Thomas and Lim, Siew Pheng (2007) Yellow fever virus NS3 protease: peptide-inhibition studies. The Journal of General Virology, 88 (Pt 8). pp. 2223-2227. ISSN 0022-1317

Abstract

A recombinant form of yellow fever virus (YFV) NS3 protease, linked via a nonapeptide to the minimal NS2B co-factor sequence (CF40-gly-NS3pro190), was expressed in Escherichia coli and shown to be catalytically active. It efficiently cleaved the fluorogenic tetrapeptide substrate Bz-norleucine-lysine-arginine-arginine-AMC, which was previously optimized for dengue virus NS2B/3 protease. A series of small peptidic inhibitors based on this substrate sequence readily inhibited its enzymic activity. To understand the structure-activity relationship of the inhibitors, they were docked into a homology model of the YFV NS2B/NS3 protease structure. The results revealed that the P1 and P2 positions are most important for inhibitor binding, whilst the P3 and P4 positions have much less effect. These findings indicate that the characteristics of YFV protease are very similar to those reported for dengue and West Nile virus proteases, and suggest that pan-flavivirus NS3 protease drugs may be developed for flaviviral diseases.

Item Type: Article
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Additional Information: free final full text version available at publisher's official URL; author can archive post-print (ie final draft post-refereeing); On author or institutional server only; Publisher's version/PDF cannot be used unless payment of fee
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Date Deposited: 14 Dec 2009 14:02
Last Modified: 31 Jan 2013 01:21
URI: https://oak.novartis.com/id/eprint/301

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