Antiviral Activity of Arbidol, a Broad-Spectrum Drug for Use Against Respiratory Viruses, Varies According to Test Conditions
Antiviral Activity of Arbidol, a Broad-Spectrum Drug for Use Against Respiratory Viruses, Varies According to Test Conditions
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DOI：
10.1002/jmv.22234
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发表时间：
2012-01-01
影响因子：
12.7
通讯作者：
Tannock, Gregory A.
中科院分区：
文献类型：
--
作者：
Brooks, Megan J.;Burtseva, Elena I.;Tannock, Gregory A.
研究了阿比朵尔对7种不同病毒家族代表的治疗活性。其半数有效浓度（EC 50）为0.22-11.8 μ g/ml（0.41-22 nM）。1型脊髓灰质炎病毒的治疗指数为91，甲型和B型流感病毒、人副粘病毒3型、鸡传染性支气管炎病毒和马立克氏病病毒的治疗指数为1.9-8.5。阿比朵尔对A/Aichi/2/68（H3 N2）流感病毒的抑制作用比金刚乙胺或金刚烷胺更强（EC 50 10 vs. >15和>31.6 μ g/ml）;当终点以TCID（50）s表示时，抑制作用更强。对于呼吸道合胞病毒（RSV），观察到空斑大小减少，但数量未减少。然而，当将药物加入感染的培养物中（>5 μ g/ml）时，滴度出现3-log下降。阿比朵尔不直接抑制流感A/Aichi/2/68血凝素（HA）或神经氨酸酶（NA）活性，但当在感染前以0.1 μ g/ml加入时，病毒包膜和鸡红细胞之间的融合受到抑制。阿比朵尔诱导感染流感A/PR/8/34的MDCK培养物中PB 2、PA、NP、NA和NS基因的病毒mRNA合成发生变化。没有间接证据表明阿比朵尔在感染A/Aichi/2/68后增强了干扰素-α。阿比朵尔在通过口服和腹膜内（i. p.）途径和用流感A/Aichi/2/68鼻内激发。在i. p.给药和随后的RSV攻毒后，肺实变略有降低，但病毒滴度未降低。结果表明阿比朵尔作为广谱呼吸道抗病毒药物的潜力。J. Med. Virol. 84：170-181，2012. (C)2011 Wiley Periodicals，Inc.
The therapeutic activity of arbidol was investigated against representatives of seven different virus families. Its 50% median effective concentration (EC50) was 0.22-11.8 mu g/ml (0.41-22 nM). Therapeutic indices of 91 were obtained for type 1 poliovirus and 1.9-8.5 for influenza A and B, human paramyxo-3, avian infectious bronchitis-, and Marek's disease viruses. Arbidol was more inhibitory for influenza A/Aichi/2/68 (H3N2) virus than rimantadine or amantadine (EC50 10 vs. >15 and >31.6 mu g/ml); greater inhibition occurred when end-points were expressed as TCID(50)s. For respiratory syncytial virus (RSV), a reduction in plaque size but not number was observed. However, when the drug was added to infected cultures (>5 mu g/ml), a 3-log reduction in titer occurred. Arbidol did not inhibit directly influenza A/Aichi/2/68 hemagglutinin (HA) or neuraminidase (NA) activity, but inhibition of fusion between the viral envelope and chicken red blood cells occurred when added at 0.1 mu g/ml prior to infection. Arbidol induced changes to viral mRNA synthesis of the PB2, PA, NP, NA, and NS genes in MDCK cultures infected with influenza A/PR/8/34. There was no indirect evidence of enhancement of interferon-alpha by arbidol following infection with A/Aichi/2/68. Arbidol neither reduced lung viral titers nor caused a significant reduction of lung consolidation in BALB/c mice after administration by the oral and intraperitoneal (i.p.) routes and intranasal challenge with influenza A/Aichi/2/68. A small reduction in lung consolidation, but not viral titer, occurred after i.p. administration and subsequent challenge with RSV. The results indicate the potential of arbidol as a broad-spectrum respiratory antiviral drug. J. Med. Virol. 84:170-181, 2012. (C) 2011 Wiley Periodicals, Inc.