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Spectrum of antiviral activity of 4-aminopyrimidine N-oxides against a broad panel of tick-borne encephalitis virus strains

机译:4-氨基嘧啶N-氧化物对近蜱传播脑炎病毒菌株的抗病毒活性的光谱

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摘要

Tick-borne encephalitis is an important human arbovirus neuroinfection spread across the Northern Eurasia. Inhibitors of tick-borne encephalitis virus (TBEV) strain Absettarov, presumably targeting E protein n-octyl-β-d-glucoside (β-OG) pocket, were reported earlier. In this work, these inhibitors were tested in vitro against seven strains representing three main TBEV subtypes. The most potent compound, 2-[(2-methyl-1-oxido-5,6,7,8-tetrahydroquinazolin-4-yl)amino]-phenol, showed EC50 values lower than 22 µM against all the tested strains. Nevertheless, EC50 values for virus samples of certain strains demonstrated a substantial variation, which appeared to be consistent with the presence of E protein not only in infectious virions, but also in non-infectious and immature virus particles, protein aggregates, and membrane complexes.
机译:蜱型脑炎是欧亚北部北部蔓延的重要人类arbovirus neuroinfection。提前报道,蜱型脑炎病毒(TBEV)菌株Absettarov的抑制剂(TBEV)菌株Absettarov,旨在靶向E蛋白N-辛基-β-D-葡糖苷(β-OG)口袋。在这项工作中,这些抑制剂在体外测试了七个代表三个主要TBEV亚型的菌株。最有效的化合物,2 - [(2-甲基-1-氧基-5,6,6,7,8-四氢喹唑啉-4-基)氨基] -phenol,显示EC50值低于22μm的所有测试菌株。然而,某些菌株病毒样品的EC50值证明了大量的变异,这似乎与E蛋白的存在不仅在传染病中存在,而且在非传染性和未成熟的病毒颗粒,蛋白质聚集体和膜复合物中均匀。

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