The use of sialidase therapy for respiratory viral infections

被引:38
作者
Nicholls, John M. [1 ]
Moss, Ronald B. [2 ]
Haslam, Stuart M. [3 ]
机构
[1] Univ Hong Kong, Dept Pathol, Pok Fu Lam, Hong Kong, Peoples R China
[2] Ansun BioPharma, San Diego, CA 92121 USA
[3] Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Div Mol Biosci, London SW7 2AZ, England
关键词
Influenza; Antiviral therapy; Sialidase; Sialic acid; INFLUENZA-VIRUS INFECTION; HUMAN AIRWAY EPITHELIUM; HOST-CELL RECEPTOR; FUSION PROTEIN; STREPTOCOCCUS-PNEUMONIAE; DROPLET TRANSMISSION; ACTINOMYCES-VISCOSUS; PARAINFLUENZA VIRUS; EXPERIMENTAL DRUG; O-ACETYLATION;
D O I
10.1016/j.antiviral.2013.04.012
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
DAS181 is an inhaled bacterial sialidase which functions by removing sialic acid (Sia) from the surface of epithelial cells, preventing attachment and subsequent infection by respiratory viruses that utilize Sia as a receptor. DAS181 is typical of bacterial sialidases in cleaving Sia alpha 2-3 and Sia alpha 2-6 linkages, and it also has a demonstrated effect against acetylated and hydroxylated forms of Sia. The potency of the compound has been enhanced by coupling the active sialidase with an amphiregulin tag, allowing a longer duration of action and minimizing spread to the systemic circulation. DAS181 is now in Phase II development for the treatment of influenza, and it has also demonstrated activity in individual cases of parainfluenza in immunosuppressed patients. Continued evaluation of the roles and activities of bacterial sialidases is required to expand the range of successful antiviral therapies targeting Sia or its derivatives. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:401 / 409
页数:9
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