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Antimicrobial Agents and Chemotherapy, September 2009, p. 3935-3941, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00389-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

DAS181 Inhibits H5N1 Influenza Virus Infection of Human Lung Tissues {triangledown}

Renee W. Y. Chan,1,2,{dagger} Michael C. W. Chan,1,{dagger} Adam C. N. Wong,2 Rositsa Karamanska,4 Anne Dell,4 Stuart M. Haslam,4 Alan D. L. Sihoe,3 W. H. Chui,3 Gallen Triana-Baltzer,5 Qixiang Li,5 J. S. Malik Peiris,1 Fang Fang,5* and John M. Nicholls2*

Departments of Microbiology,1 Pathology,2 Cardiothoracic Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR,3 Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom,4 NexBio, Inc., 10665 Sorrento Valley Road, San Diego, California 921215

Received 23 March 2009/ Returned for modification 28 April 2009/ Accepted 1 July 2009

DAS181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing the virus receptor, sialic acid (Sia), from the adjacent glycan structures. DAS181 and its analogues have previously been shown to be potently active against multiple strains of seasonal and avian influenza virus strains in several experimental models, including cell lines, mice, and ferrets. Here we demonstrate that DAS181 treatment leads to desialylation of both {alpha}2-6-linked and {alpha}2-3-linked Sia in ex vivo human lung tissue culture and primary pneumocytes. DAS181 treatment also effectively protects human lung tissue and pneumocytes against the highly pathogenic avian influenza virus H5N1 (A/Vietnam/3046/2004). Two doses of DAS181 treatment given 12 h apart were sufficient to block H5N1 infection in the ex vivo lung tissue culture. These findings support the potential value of DAS181 as a broad-spectrum therapeutic agent against influenza viruses, especially H5N1.

* Corresponding author. Mailing address for John M. Nicholls: Department of Pathology, The University of Hong Kong, Pok Fu Lam, Hong Kong. Phone: 852-28554883. Fax: 852-28725197. E-mail: nicholls{at}pathology.hku.hk. Mailing address for Fang Fang: NexBio, Inc., 10665 Sorrento Valley Road, San Diego, CA 92121. Phone: (858) 452-2631. Fax: (858) 452-2534. E-mail: ffang{at}nexbio.com

{triangledown} Published ahead of print on 13 July 2009.

{dagger} Renee W. Y. Chan and Michael C. W. Chan contributed equally to this report.

Antimicrobial Agents and Chemotherapy, September 2009, p. 3935-3941, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00389-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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