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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Alkylated porphyrins have broad antiviral activity against hepadnaviruses, flaviviruses, filoviruses, and arenaviruses.
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Alkylated porphyrins have broad antiviral activity against hepadnaviruses, flaviviruses, filoviruses, and arenaviruses.

机译：烷基化的卟啉对肝炎病毒，黄病毒，丝状病毒和沙粒病毒具有广泛的抗病毒活性。

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We screened approximately 2,200 compounds known to be safe in people for the ability to reduce the amount of virion-associated hepatitis B virus (HBV) DNA in the culture medium of producer cells. These efforts led to the discovery of an alkylated porphyrin, chlorophyllide, as the compound that achieved the greatest reduction in signal. Here we report that chlorophyllide directly and quantitatively disrupted HBV virions at micromolar concentrations, resulting in the loss of all detectable virion DNA, without detectably affecting cell viability or intracellular viral gene products. Chemophores of chlorophyllide were also tested. Chlorin e6, a metal-free chlorophyllide-like molecule, showed the strongest antiviral activity against HBV as well as profound antiviral effects on other enveloped viruses, such as hepatitis C virus (HCV), human immunodeficiency virus (HIV), dengue virus (DENV), Marburg virus (MARV), Tacaribe virus (TCRV), and Junin viruses (JUNV). Remarkably, chlorin e6 inactivated DENV at subnanomolar-level concentrations. However, the compound had no antiviral effect against encephalomyocarditis virus and adenovirus, suggesting that chlorin e6 may be less active or inactive against nonenveloped viruses. Although other porphyrin derivatives have been previously reported to possess antiviral activity, this is the first analysis of the biochemical impact of chlorophyllide and chlorin e6 against HBV and of the dramatic anti-infectivity impact upon DENV. The possible application of this family of compounds as antiviral agents, as microbicides and systemic virus neutralizing agents, is discussed.
机译：我们筛选了大约2,200种已知对人类安全的化合物，这些化合物能够减少生产细胞培养基中与病毒体相关的乙型肝炎病毒（HBV）DNA的数量。这些努力导致发现了烷基化的卟啉叶绿素，它是最大程度降低信号的化合物。在这里我们报告说，叶绿素直接和定量地破坏了微摩尔浓度的HBV病毒颗粒，导致所有可检测的病毒颗粒DNA丢失，而没有可检测地影响细胞活力或细胞内病毒基因产物。还测试了叶绿素的化学基团。 Chlorin e6是一种不含金属的叶绿素样分子，对HBV表现出最强的抗病毒活性，并对其他包膜病毒（如丙型肝炎病毒（HCV），人免疫缺陷病毒（HIV），登革热病毒（DENV））具有深远的抗病毒作用），马尔堡病毒（MARV），塔卡里布病毒（TCRV）和胡宁病毒（JUNV）。值得注意的是，二氢卟酚e6在亚纳摩尔水平下使DENV失活。但是，该化合物对脑心肌炎病毒和腺病毒没有抗病毒作用，表明二氢卟酚e6可能对非包膜病毒的活性较低或无活性。尽管先前已报道其他卟啉衍生物具有抗病毒活性，但这是首次分析叶绿素和二氢卟酚e6对HBV的生化影响以及对DENV的显着抗感染作用。讨论了该化合物家族作为抗病毒剂，杀微生物剂和全身性病毒中和剂的可能应用。

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