Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses.
Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses.
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DOI：
10.3390/v10040184
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发表时间：
2018-04-10
期刊：
影响因子：
--
通讯作者：
Ruzek D
中科院分区：
文献类型：
--
作者：
Haviernik J;Štefánik M;Fojtíková M;Kali S;Tordo N;Rudolf I;Hubálek Z;Eyer L;Ruzek D
节肢动物传播的黄病毒是具有全球医学重要性的人类病原体，目前尚未报道有效的小分子抗病毒疗法。阿比朵尔（umifenovir）是一种广谱抗病毒化合物，已在俄罗斯和中国批准用于预防和治疗流感。该化合物具有对抗多种 DNA 和 RNA 病毒的活性。作用方式主要基于病毒与细胞相互作用的关键步骤的受损。在这里，我们证明阿比朵尔在感染寨卡病毒、西尼罗河病毒和蜱传脑炎病毒（三种节肢动物传播黄病毒的医学上重要代表）的Vero细胞中具有微摩尔水平的抗病毒作用（EC50值范围为10.57±0.74至19.16±0.29μM）。有趣的是，在病毒感染的猪稳定肾细胞（PS）、人神经母细胞瘤细胞（UKF-NB-4）和人肝癌细胞（Huh-7细胞）中没有观察到阿比多尔的抗病毒作用，这表明阿比多尔的抗病毒作用强烈依赖于细胞类型。在各种细胞系中进行测试时，阿比朵尔显示出逐渐增加的细胞毒性，顺序为：Huh-7 < HBCA < PS < UKF-NB-4 < Vero，CC50 值范围为 18.69 ± 0.1 至 89.72 ± 0.19 µM。抗病毒活性和可接受的细胞毒性特征表明，阿比多尔可能是进一步研究的有希望的候选者，作为选择性治疗黄病毒感染的潜在治疗剂。
Arthropod-borne flaviviruses are human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy has currently been reported. Arbidol (umifenovir) is a broad-spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound shows activities against numerous DNA and RNA viruses. The mode of action is based predominantly on impairment of critical steps in virus-cell interactions. Here we demonstrate that arbidol possesses micromolar-level anti-viral effects (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of the arthropod-borne flaviviruses. Interestingly, no antiviral effects of arbidol are observed in virus infected porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-4), and human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol shows increasing cytotoxicity when tested in various cell lines, in the order: Huh-7 < HBCA < PS < UKF-NB-4 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activities and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in selective treatment of flaviviral infections.
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