Phosphonate inhibitors of West Nile virus NS2B/NS3 protease |
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| Authors: | Marcin Skoreński Aleksandra Milewska Krzysztof Pyrć Marcin Sieńczyk |
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| Institution: | 1. Faculty of Chemistry, Division of Medicinal Chemistry and Microbiology, Wroclaw University of Science and Technology, Wroclaw, Poland;2. Faculty of Biochemistry, Biophysics and Biotechnology, Microbiology Department, Jagiellonian University, Krakow, Poland;3. Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland |
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| Abstract: | West Nile virus (WNV) is a member of the flavivirus genus belonging to the Flaviviridae family. The viral serine protease NS2B/NS3 has been considered an attractive target for the development of anti-WNV agents. Although several NS2B/NS3 protease inhibitors have been described so far, most of them are reversible inhibitors. Herein, we present a series of α-aminoalkylphosphonate diphenyl esters and their peptidyl derivatives as potent inhibitors of the NS2B/NS3 protease. The most potent inhibitor identified was Cbz-Lys-Arg-(4-GuPhe)P(OPh)2 displaying Ki and k2/Ki values of 0.4 µM and 28 265 M?1s?1, respectively, with no significant inhibition of trypsin, cathepsin G, and HAT protease. |
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| Keywords: | NS2B/NS3 protease aminophosphonates serine proteases enzyme inhibitors West Nile virus |
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