Antiviral Activity of Arbidol, a Broad-Spectrum Drug for Use Against Respiratory Viruses, Varies According to Test Conditions

被引:70
作者
Brooks, Megan J. [1 ]
Burtseva, Elena I. [2 ]
Ellery, Philip J. [3 ]
Marsh, Glenn A. [1 ]
Lew, Andrew M. [4 ]
Slepushkin, Anatoly N. [2 ]
Crowe, Suzanne M. [3 ]
Tannock, Gregory A. [1 ,3 ]
机构
[1] RMIT Univ, Dept Biotechnol & Environm Biol, Bundoora, Vic, Australia
[2] Russian Acad Med, DI Ivanovsky Res Inst Virol, Moscow, Russia
[3] Burnet Inst, Ctr Virol, Melbourne, Vic, Australia
[4] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
关键词
respiratory; antiviral; broad-spectrum; conditions; INFLUENZA-A VIRUSES; NEURAMINIDASE INHIBITORS; IN-VITRO; SEASONAL PROPHYLAXIS; SYNCYTIAL VIRUS; INTERFERON; RESISTANCE; MICE; OSELTAMIVIR; INFECTIONS;
D O I
10.1002/jmv.22234
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页码:170 / 181
页数:12
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