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
相关论文
共 47 条
[31]  
PALMER DF, 1975, ADV LAB TECHNIQUES I, P25
[32]   Inhibition of influenza A virus replication by compounds interfering with the fusogenic function of the viral hemagglutinin [J].
Plotch, SJ ;
O'Hara, B ;
Morin, J ;
Palant, O ;
LaRocque, J ;
Bloom, JD ;
Lang, SA ;
DiGrandi, MJ ;
Bradley, M ;
Nilakantan, R ;
Gluzman, Y .
JOURNAL OF VIROLOGY, 1999, 73 (01) :140-151
[33]   PILOT-STUDY OF RECOMBINANT INTERFERON ALPHA-2A FOR TREATMENT OF INFANTS WITH BRONCHIOLITIS INDUCED BY RESPIRATORY SYNCYTIAL VIRUS [J].
PORTNOY, J ;
HICKS, R ;
PACHECO, F ;
OLSON, L .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1988, 32 (04) :589-591
[34]  
REED L. J., 1938, AMER JOUR HYG, V27, P493
[35]   Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008 [J].
Sheu, Tiffany G. ;
Deyde, Varough M. ;
Okomo-Adhiambo, Margaret ;
Garten, Rebecca J. ;
Xu, Xiyan ;
Bright, Rick A. ;
Butler, Ebonee N. ;
Wallis, Teresa R. ;
Klimov, Alexander I. ;
Gubareva, Larisa V. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2008, 52 (09) :3284-3292
[36]   Antiviral activity of arbidol against influenza A virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo [J].
Shi, L. ;
Xiong, H. ;
He, J. ;
Deng, H. ;
Li, Q. ;
Zhong, Q. ;
Hou, W. ;
Cheng, L. ;
Xiao, H. ;
Yang, Z. .
ARCHIVES OF VIROLOGY, 2007, 152 (08) :1447-1455
[37]   BROAD-SPECTRUM ANTIVIRAL ACTIVITY OF VIRAZOLE - 1-BETA-D-RIBOFURANOSYL-1,2,4-TRIAZOLE-3-CARBOXAMIDE [J].
SIDWELL, RW ;
WITKOWSKI, JT ;
ALLEN, LB ;
ROBINS, RK ;
KHARE, GP ;
HUFFMAN, JH .
SCIENCE, 1972, 177 (4050) :705-+
[38]   Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor [J].
Sidwell, RW ;
Huffman, JH ;
Barnard, DL ;
Bailey, KW ;
Wong, MH ;
Morrison, A ;
Syndergaard, T ;
Kim, CU .
ANTIVIRAL RESEARCH, 1998, 37 (02) :107-120
[39]   Comparison of colorimetric, fluorometric, and visual methods for determining anti-influenza (H1N1 and H3N2) virus activities and toxicities of compounds [J].
Smee, DF ;
Morrison, AC ;
Barnard, DL ;
Sidwell, RW .
JOURNAL OF VIROLOGICAL METHODS, 2002, 106 (01) :71-79
[40]   Cyclopentane neuraminidase inhibitors with potent in vitro anti-influenza virus activities [J].
Smee, DF ;
Huffman, JH ;
Morrison, AC ;
Barnard, DL ;
Sidwell, RW .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (03) :743-748