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具有强大抗流感病毒活性的奥司他韦类似物。

Oseltamivir analogs with potent anti-influenza virus activity.

机构信息

Department of Chemistry, Miranda House University Enclave, University of Delhi, Delhi, 110007, India.

Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College University Enclave, University of Delhi, Delhi, 110007, India; Loyola University Stritch School of Medicine, 2160 South First Avenue, Chicago, IL, USA.

出版信息

Drug Discov Today. 2020 Aug;25(8):1389-1402. doi: 10.1016/j.drudis.2020.06.004. Epub 2020 Jun 15.

Abstract

Influenza A and B viruses cause seasonal worldwide influenza epidemics each winter, and are a major public health concern and cause of morbidity and mortality. A substantial reduction in influenza-related deaths can be attributed to both vaccination and administration of oseltamivir (OS), which is approved for oral administration and inhibits viral neuraminidase (NA), a transmembrane protein. OS carboxylate (OSC), the active form of OS, is formed by the action of endogenous esterase, which targets NA and is shown to significantly reduce influenza-related deaths. However, the development of resistance in various viral variants, including H3N2 and H5N1, has raised concern about the effectiveness of OS. This comprehensive review covers a range of OS analogs shown to be effective against influenza virus, comparing different types of substituent group that contribute to the activity and bioavailability of these compounds.

摘要

甲型和乙型流感病毒每年冬季都会在全球引发季节性流感疫情,是主要的公共卫生关注点,也是发病率和死亡率的主要原因。流感相关死亡人数的大幅减少归因于疫苗接种和奥司他韦(OS)的使用,OS 经批准用于口服给药并抑制病毒神经氨酸酶(NA),一种跨膜蛋白。OS 羧酸酯(OSC)是 OS 的活性形式,由内源性酯酶作用形成,该酯酶靶向 NA,可显著降低流感相关死亡人数。然而,各种病毒变体(包括 H3N2 和 H5N1)出现耐药性,这引起了对 OS 有效性的担忧。本综述涵盖了一系列被证明对流感病毒有效的 OS 类似物,比较了不同类型的取代基,这些取代基有助于这些化合物的活性和生物利用度。

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