西尼罗河病毒 NS2B/NS3 蛋白酶的膦酸酯抑制剂。
Phosphonate inhibitors of West Nile virus NS2B/NS3 protease.
机构信息
a Faculty of Chemistry, Division of Medicinal Chemistry and Microbiology , Wroclaw University of Science and Technology , Wroclaw , Poland.
b Faculty of Biochemistry, Biophysics and Biotechnology, Microbiology Department , Jagiellonian University , Krakow , Poland.
出版信息
J Enzyme Inhib Med Chem. 2019 Dec;34(1):8-14. doi: 10.1080/14756366.2018.1506772.
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)(OPh) displaying K and k/K values of 0.4 µM and 28 265 Ms, respectively, with no significant inhibition of trypsin, cathepsin G, and HAT protease.
西尼罗河病毒（WNV）是黄病毒属的一员，属于黄病毒科。病毒丝氨酸蛋白酶 NS2B/NS3 一直被认为是开发抗 WNV 药物的有吸引力的靶标。尽管迄今为止已经描述了几种 NS2B/NS3 蛋白酶抑制剂，但它们大多数都是可逆抑制剂。在此，我们提出了一系列 α-氨基烷基膦酸二苯酯及其肽基衍生物，作为 NS2B/NS3 蛋白酶的有效抑制剂。鉴定出的最有效的抑制剂是 Cbz-Lys-Arg-(4-GuPhe)(OPh)，其 K 和 k/K 值分别为 0.4 µM 和 28 265 Ms，对胰蛋白酶、组织蛋白酶 G 和 HAT 蛋白酶没有明显抑制作用。
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