Institute of Poliomyelitis and Viral Encephalitides, FSBSI Chumakov FSC R&D IBP RAS, Poselok Instituta Poliomielita, Moscow, Russian Federation.
Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
Arch Pharm (Weinheim). 2018 Jun;351(6):e1700353. doi: 10.1002/ardp.201700353. Epub 2018 Apr 30.
Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, is the leading cause of arboviral neuroinfections in Europe. Only a few classes of the nucleoside and non-nucleoside inhibitors were investigated against TBEV reproduction. Paving the way to previously unexplored areas of anti-TBEV chemical space, we assessed the inhibition of TBEV reproduction in the plaque reduction assay by various compounds derived from cyanothioacetamide and cyanoselenoacetamide. Compounds from seven classes, including 4-(alkylthio)-2-aryl-3-azaspiro[5.5]undec-4-ene-1,1,5-tricarbonitriles, 3-arylamino-2-(selenazol-2-yl)acrylonitriles, ethyl 6-(alkylseleno)-5-cyano-2-oxo-1,2-dihydropyridine-3-carboxylates, 6-(alkylseleno)-2-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles, 2-(alkylseleno)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitriles, 8-selenoxo-3,5,7,11-tetraazatricyclo[7.3.1.0 ]tridec-2-ene-1,9-dicarbonitriles, and selenolo[2,3-b]quinolines, inhibited TBEV reproduction with EC values in the micromolar range while showing moderate cytotoxicity and no inhibition of enterovirus reproduction. Thus, new scaffolds with promising anti-TBEV activity were found.
蜱传脑炎病毒（TBEV）是黄病毒属的一员，是欧洲虫媒病毒性脑炎的主要病原体。仅有少数几类核苷类和非核苷类抑制剂被用于研究 TBEV 的复制。为了开拓抗 TBEV 化学空间的未知领域，我们评估了从氰硫乙酰胺和氰硒乙酰胺衍生而来的各种化合物在噬斑减少试验中对 TBEV 复制的抑制作用。有七个类别的化合物，包括 4-（烷基硫代）-2-芳基-3-氮杂螺[5.5]十一-4-烯-1,1,5-三氰基，3-芳基氨基-2-（硒唑-2-基）丙烯腈，乙基 6-（硒代烷基）-5-氰基-2-氧代-1,2-二氢吡啶-3-羧酸酯，6-（硒代烷基）-2-氧代-1,4,5,6-四氢吡啶-3-甲腈，2-（硒代烷基）-5-氧代-1,4,5,6,7,8-六氢喹啉-3-甲腈，8-硒代氧-3,5,7,11-四氮杂三环[7.3.1.0]十三-2-烯-1,9-二甲腈和硒唑并[2,3-b]喹啉，这些化合物以微摩尔浓度范围抑制 TBEV 复制，同时显示出中等细胞毒性，且不抑制肠道病毒复制。因此，发现了具有抗 TBEV 活性的新骨架。
